Computer-based assessment of movement difficulties in Parkinson's disease

The prevalence of Parkinson's disease (PD) is increasing due to an ageing population. It is an unpredictable disease which requires regular assessment and monitoring. Current techniques used to assess PD are subjective. Clinicians observe movements made by a patient and subsequently rate the level of severity of, for example tremor or slowness of movement. Within this work, we have developed and evaluated a prototype computer-based assessment tool capable of collecting information on the movement difficulties present in PD. Twenty participants took part in an assessment of the tool, 10 of whom were diagnosed with PD and 10 were without the disease. Following the usage of the tool, it was found that there was a significant difference (p?=?0.038) in the speed of movement between the two groups. We envisage that this tool could have the potential to enable more objective clinical conclusions to be made.     

Should evolutionary history guide conservation?

Phylogenetic diversity (PD) is an emerging tool for prioritising species in biodiversity conservation problems. PD uses the evolutionary history of a group of species to provide a formal measure of their biodiversity. This provides an objective target for biodiversity conservation, in which decisions are frequently made for political reasons or according to the charisma of a species. Incorporating PD in biodiversity decisions ensures that the best outcome given current knowledge is achieved. Unfortunately, the phylogenetic information required to calculate PD is frequently unknown or costly to obtain. Using PD in a decision making framework also complicates the process substantially, thereby decreasing its transparency and potentially disillusioning stakeholders. Here we provide a broad assessment of the value of PD in biodiversity conservation approaches. We find that using PD in a prioritisation process can typically increase biodiversity outcomes by a broad range of 10–220 %. Higher gains are obtained where (i) few species are selected, (ii) the phylogeny includes speciation events on a broad range of time scales and/or (iii) closely related species are prioritised in the absence of PD (e.g. several closely related charismatic animals). Our results indicate situations where PD is likely to contribute substantially to biodiversity conservation decisions and provides guidance to organisations when deciding whether to incorporating phylogenetic information in their decision making. This assessment is crucial as inclusion of PD may be costly and reduces transparency of the decision process, however the potential gains may far outweigh this cost.     

Bioaccessibility-Based Risk Assessment of PAHs in Soils from Sites of Different Anthropogenic Activities in Lagos,Nigeria Using the Fed Organic Estimation Human Simulation Test Method

The aim of this study was to carry out a bioaccessibility-based risk assessment of polycyclic aromatic hydrocarbons (PAHs) in soils from sites of different anthropogenic activities in Lagos, Nigeria. Using an in vitro gastrointestinal model—Fed Organic Estimation Human Simulation Test method (FOREShT), the concentration of bioaccessible 16 priority US Environmental Protection Agency (USEPA) PAHs in soils were determined. Total concentration of 16 priority USEPA PAHs was also determined. The concentration range was 702–253,922 ng g^?1 and 92–760 ng g^?1 for total and bioaccessible PAHs, respectively. For persons involved with activities at these sites no health risks were observed, based on bioaccessibility values of PAHs. Mean daily intake of PAHs from these soils were below the oral mean daily intake threshold for PAHs in food. Also, overall estimated theoretical cancer risk (2.5 × 10^?09, 6.5 × 10^?07, 5.5 × 10^?10, 2.7 × 10^?09, 6.5 × 10^?10, 9.5 × 10^?10, 2.0 × 10^?09, and 4.1 × 10^?07 for the eight sites based on their bioaccessible concentration) for exposure to PAHs in surface soils were below the health guidelines for extreme (1 × 10^?04) and normal (1 × 10^?06) exposures.     

Caffeine reversal of sleep deprivation effects on alertness,mood and repeated sprint performances in physical education students

The aim of this study was to evaluate the effects of caffeine ingestion and partial sleep deprivation on mood and cognitive and physical performances. In randomised order, 12 healthy male physical education students completed four test sessions at 18:00 h after placebo or 5 mg/kg of caffeine ingestion during a baseline night (RN) (bed time: from 22:00 to 07:00 h), or during a night of partial (four hrs) sleep deprivation (PSD). During each test session, participants performed a reaction time test, a vigilance test, the 10 s Wingate cycling test during (measuring peak power (PP) and anaerobic capacity), and the 5 m multiple shuttle test (measuring peak distance (PD), total distance (TD), and fatigue index (FI)). Compared to RN, simple reaction time, vigilance, PP, PD, TD, and FI were altered by PSD the following day after placebo ingestion with increased reaction time and FI and reduced PP, PD, TD, and vigilance (p < 0.001). Moreover, during PSD condition, PP, PD, and TD were significantly higher after caffeine ingestion in comparison with placebo ingestion (p < 0.05). However, both simple reaction times and vigilance were significantly lower after caffeine ingestion in comparison with placebo during PSD (p < 0.05). Caffeine is an effective strategy to maintain physical and cognitive performances the day after PSD.     

Variations in rest-activity rhythm are associated with clinically measured disease severity in Parkinson’s disease

ABSTRACT

The continuous, longitudinal nature of accelerometry monitoring is well-suited to capturing the regular 24-hour oscillations in human activity across the day, the cumulative effect of our circadian rhythm and behavior. Disruption of the circadian rhythm in turn disrupts rest-activity rhythms. Although circadian disruption is a major feature of Parkinson’s disease (PD), rest-activity rhythms and their relationship with disease severity have not been well characterized in PD. 13 PD participants (Hoehn & Yahr Stage [H&Y] 1–3) wore a Philips Actiwatch Spectrum PRO continuously for two separate weeks. Rest-activity rhythms were quantified by fitting an oscillating 24-hour cosinor model to each participant-day of activity data. One-way ANOVAs adjusted for demographics revealed significant variation in the amount (MESOR, F = 12.76, p < .01), range (Amplitude, F = 9.62, p < .01), and timing (Acrophase, F = 2.7, p = .05) of activity across H&Y Stages. Those with higher H&Y Stages were significantly more likely to be active later in the day, where-as those who shifted between H&Y Stages during the study were significantly more active than those who did not change H&Y Stage. Being active later in the day was also significantly associated with higher scores on the Movement Disorder Society’s Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Section III (motor symptom severity, p = .02), Section II (self-reported impact of motor symptoms on daily living, p = .01), and Total Score (p = .01) in an adjusted linear regression model; significant associations between MDS-UPDRS scores and activity levels were observed only in the unadjusted model. These findings demonstrate that continuous actigraphy is capable of detecting rest-activity disruption in PD, and provides preliminary evidence that rest-activity rhythms are associated with motor symptom severity and H&Y Stage.     

Application of the Hands-On Donkey Tool for Assessing the Welfare of Working Equids at Tuliman,Mexico

Equids are still used for diverse chores in Mexico and are essential for the livelihoods of numerous families. Appropriate health and behavior are prerequisites for performing work without affecting welfare. This study aimed to assess the welfare of working equids in Tuliman, applying the hands-on donkey tool. This tool evaluates five dimensions (behavior, body condition score [BCS], wounds, lameness, and other health issues) and was applied to 438 working equids (horses, mules, and donkeys). The Kruskall-Wallis test was applied to investigate differences between species and sex. Donkeys were more common; they also presented more positive behaviors and less lameness (p < 0.05). No differences were found for BCS among species on a scale ranging from 1 to 5 (mean BCS for donkeys = 1.9; mules = 2; and horses = 1.8). Mares had significantly lower BCS (mean = 1.5) than stallions (p < 0.05) and geldings (mean = 1.9). Overall mules had better welfare evaluations. The tool allowed detection of welfare issues in working equids; a practical outcome would be implementing local welfare strategies according to its results.     

Association Between Serum Zinc Levels and the Risk of Parkinson’s Disease: a Meta-Analysis

Recent studies have found that the serum zinc levels were associated with the risk of Parkinson’s disease (PD), but the results were inconsistent. Thus, we conducted a meta-analysis to summarize the evidence from observational studies between them. Pertinent studies were identified by a search in PubMed, Embase, and Web of science up to July, 10, 2016. Standardized mean difference (SMD) and 95% confidence intervals (CI) with random-effect model was used to combine the results. Subgroup analysis and meta-regression were also conducted. Publication bias was estimated using Begg’s regression asymmetry test. A total of 11 articles involving 822 PD patients and 777 healthy controls were included in the meta-analysis. Our meta-analysis results revealed that the serum zinc levels in PD patients were significantly lower than those in health controls (SMD = ?0.779, 95%CI = [?1.323, ?0.234], P < 0.001). The association was also significant oriental studies (SMD = ?1.601, 95%CI = [?2.398, ?0.805], P < 0.001). No publication bias was found. The current study indicated that serum zinc levels in PD patients were significantly lower than those in healthy controls.     

Focal Electrical Stimulation as an Effective Sham Control for Active rTMS and Biofeedback Treatments

A valid sham control is important for determining the efficacy and effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an experimental and clinical tool. Given the manner in which rTMS is applied, separately or in combination with self-regulatory approaches, and its intended impact on brain states, a valid sham control of this type may well serve as a meaningful control for biofeedback studies, where efforts to develop a credible control have often been less than ideal. This study examined the effectiveness of focal electrical stimulation of the frontalis muscle as a sham technique for blinding participants to high-frequency rTMS over the dorso-lateral prefrontal cortex (DLPFC) at durations, intensities, and schedules of stimulation similar to many clinical applications. In this within-subjects single blind design, 19 participants made guesses immediately after receiving 54 counterbalanced rTMS sessions (sham, 10 Hz, 20 Hz); 7 (13 %) of the guesses were made for sham, 31 (57 %) were made for 10 Hz, and 16 (30 %) were made for 20 Hz. Participants correctly guessed the sham condition 6 % (CI 1, 32 %) of the time, which is less than the odds of chance (i.e., of guessing at random, 33 %); correctly guessed the 10 Hz condition 66 % (CI 43, 84 %) of the time, which was greater than chance; and correctly guessed the 20 Hz condition 41 % (CI 21, 65 %) of the time, which was no different than chance. Focal electrical stimulation therefore can be an effective sham control for high-frequency rTMS of the DLPFC, as well as for active biofeedback interventions. Participants were unaware that electrical stimulation was, in fact, sham rTMS.     

Response of urinary purine derivatives excretion to different levels of ruminal glucose infusion in heifers

This study investigated the response of urinary purine derivatives (PD) excretion to increasing levels of intraruminal glucose infusion to evaluate how well this indicator reflects induced changes in microbial crude protein flow. Four rumen-cannulated heifers (482 ± 25 kg body weight) were fed at maintenance energy level with a basal diet (on fresh matter basis) of 4 kg/d hay, 1.5 kg/d concentrate and 60 g/d minerals in two equal meals. The trial comprised a control period (Control I) without glucose infusion followed by four consecutive periods in which all animals received 125 g, 250 g, 500 g or 1000 g/d of glucose, respectively. For this, daily dosages of glucose and urea (90 g/d during all periods) were divided into three portions that were dissolved in water and directly administered into the rumen during morning and afternoon feedings and once during noon. After the highest glucose dosage, a second control period was carried out (Control II). Urinary PD excretion increased with glucose infusion of 125 g/d (71.4 mmol/d) and 1000 g/d (74.2 mmol/d) over the level at Control I (53.9 mmol/d (standard error of the mean (SEM) 3.4; p = 0.012). After withdrawing glucose infusion, PD excretion (79.0 mmol/d) did not return to Control I level (p = 0.001). In contrast, faecal nitrogen (N) excretions linearly increased with incremental glucose infusion (p < 0.001) from 33.9 g/d at Control I to 39.7 g/d (SEM 0.5) at 1000 g/d of glucose and were similar in Control I and II (p = 0.086). The contradicting responses in the excretions of faecal N and urinary PD to increasing glucose infusions highlight the limited accuracy of the PD excretion as a non-invasive indicator when incremental dosages of rapidly fermentable carbohydrates are supplied.     

Human health risks associated with heavy metals in soil in different areas of San Luis Potosí, México

The aim of this study was to develop a health risk assessment in different areas of San Luis Potosí, México. Four heavy metals (arsenic, mercury, cadmium, and lead) were analyzed in soil from communities assessed. The mean arsenic concentration was significantly higher (p < .05) in the city of San Luis Potosí (51.85 mg/kg) compared to the other assessed areas (5.52–8.43 mg/kg). For cadmium, the mean concentration was significantly higher (p < .05) in Santa Maria Picula (7.46 mg/kg) than in the other areas (3.72–4.15 mg/kg). Regarding mercury levels, a significantly higher (p < .05) mean concentration was found in Mezquitic (1.54 mg/kg) compared to other areas (0.56–0.81 mg/kg). Lastly, when comparing the mean lead concentration in the city of San Luis Potosí (108 mg/kg), it was found to be significantly lower (p < .05) than in other areas (219–227 mg/kg). Subsequently, a probabilistic health risk assessment was performed, ingestion was the major exposure pathway for all four metals. Maximum cumulative hazard index (HI) values showed higher risk in all sampled locations (HIs > 1.0), suggesting that these sites can pose a non-carcinogenic risk to the populations (children) living in those areas. This study highlights the necessity of establishing a biomonitoring program for the surveillance of the child populations living in the assessed locations.     

Automated Hazard Assessment Techniques Using Satellite Images Following the 2008 Sichuan China Earthquake

Rapid seismic hazard assessment is crucial for accurate damage estimation right after earthquakes. New technologies provide faster damage detection compared to the traditional, manual assessments. One of the new technologies includes using satellite images. Pre- and post-earthquake satellite images can be used to identify damage patterns. One of the recent disastrous earthquakes occurred in Sichuan (M_w = 7.9) on May 12, 2008. Records show that 5 million buildings have collapsed, and more than 21 million buildings were damaged. This article presents an approach for earthquake hazard assessment using a change detection method applied to pre- and post-earthquake satellite imagery of Sichuan. The damage inspection for the identified areas was carried out performing image analysis of the pre- and post-event satellite images. In this study, a novel automated image analysis technique was developed to assess the impact of the earthquake on the flooding of the area's rivers as well as the tectonic movement of mountains. The technique was used to quantify the flooding and movement of mountains in Sichuan right after the earthquake. The proposed methodology utilizes satellite images and may potentially be used as a rapid procedure to quantify damage soon after an earthquake.     

Highly efficient in vitro proliferation and genetic stability analysis of micropropagated Ceropegiaevansii by RAPD and ISSR markers: A critically endangered plant of Western Ghats

Ceropegiaevansii McCann (family: Asclepiadaceae), a critically endangered plant of Western Ghats has acquired significant importance due to its medicinal implications, edible tubers, and ornamental flowers. This study deals with the optimization of axillary bud proliferation using nodal explants followed by genetic stability analysis of regenerants. Maximum number of shoots (11.6 ± 1.1) was observed on the Murashige and Skoog (MS) medium supplemented with 6-benzylaminopurine (4.0 mg/l) and indole-3-acetic acid (0.3 mg/l) with 85% shoot multiplication frequency. In vitro-grown shoots were rooted best in 1/2 MS medium supplemented with indole-3-butyric acid (1.0 mg/l) with an average of 10.3 ± 0.9 roots per shoot and 92% rooting frequency. Plantlets were acclimatized best (90%) in a mixture of sterile soil, sand, and coco peat (1:2:1). Micropropagated plants were subjected to random amplified polymorphic DNA and inter simple sequence repeat markers analyses. Collectively, 759 bands were generated which were monomorphic and similar to the mother plant. Findings of this study are the first report on micropropagation and assessment of genetic stability of micropropagated plantlets in C. evansii which suggests that axillary shoot proliferation can safely be used as an effective tool for propagation and conservation of C. evansii.     

Usefulness of 10 genomic regions in soybean associated with sudden death syndrome resistance

Sudden death syndrome (SDS) is an important soybean [Glycine max (L) Merrill] disease caused by the soilborne fungus Fusarium virguliforme. Currently, 14 quantitative trait loci (QTL) had been confirmed associated with resistance or tolerance to SDS. The objective of the study was to evaluate usefulness of 10 of these QTL in controlling disease expression. Six populations were developed providing a total of 321 F2-derived lines for the study. Recombinant inbred lines (RIL) used as parents were obtained from populations of ‘Essex’ × ‘Forrest’ (EF), ‘Flyer’ × ‘Hartwig’ (FH), and ‘Pyramid’ × ‘Douglas’ (PD). Disease resistance was evaluated in the greenhouse at three different planting times, each with four replications, using sorghum infested with F. virguliforme homogeneously mixed in the soil (Luckew et al., Crop Sci 52:2215–2223, 2012). Four disease assessment criteria—foliar disease incidence (DI), foliar leaf scorch disease severity (DS), area under the disease progress curve (AUDPC), and root rot severity—were used. QTL were identified in more than one of the disease assessment criteria, mainly associated with lines in the most resistant categories. Five QTL (qRfs4, qRfs5, qRfs7, qRfs12, and Rfs16) were associated with at least one of the disease assessments across multiple populations. Of the five, qRfs4 was associated with DI, AUDPC, and root rot severity, and Rfs16 with AUDPC and root rot severity. The findings suggest it may be possible for plant breeders to focus on stacking a subset of the previously identified QTL to improve resistance to SDS in soybean.     

Postural sway parameters using a triaxial accelerometer: comparing elderly and young healthy adults

The purpose of this study was to evaluate the sensitivity of 16 parameters derived from acceleration to detect changes caused by age and visual conditions during quiet standing and detect and minimise possible sources of unwanted variability that could affect accelerometer measures on the trunk. Twenty-seven healthy subjects, including 16 elderly (age, 69.3 ± 3.6 years) and 11 young (age, 23.6 ± 2.2 years) subjects, were evaluated. The parameters evaluated include root-mean-square values, fractal dimensions, path length, range, frequency dispersion and power spectrum among others derived from these values. These 16 parameters evaluated for each axis of movement and/or derivations resulted in 59 sub-parameters. These 59 sub-parameters were analysed in the elderly and young groups and under the open-eye and closed-eye conditions. The results showed that 30 sub-parameters detected differences for an age effect with open eyes, 18 detected differences with closed eyes, 25 detected differences for the young group standing with closed–open eyes and 37 detected differences for the elderly with closed and open eyes (p < 0.01). We used simple signal processing for the accelerometry signals to minimise the effects of unwanted variability that could affect the results. The results showed better performance compared with those results published previously using force platforms to evaluate postural sway. The results presented here should be useful for researchers who want to use accelerometry to evaluate steady postural balance.     

Assessment of Consequences of Notifiable Fish Disease Incursions in England and Wales

A consequence assessment framework was developed to evaluate the economic and environmental consequences of an exotic disease in the context of supporting policy level decisions on mitigation strategies. The framework adopted a semi-qualitative analysis of impacts supported by expert judgement. The efficacy of the framework was illustrated via assessment of the notifiable fish disease, Gyrodactylus salaris. In this example, the economic cost of an illustrative outbreak of G. salaris ranged from £0.22 million to £90 million. The cost of the most likely scenario (regional spread) was estimated to be £7.5 million (minimum to maximum range of £2–22 million), reflecting the uncertainty in the extent of spread of the parasite before detection. The environmental impacts vary by a factor of 35 between incursion scenarios reflecting the number of affected catchments in the scenarios.     

Parkinson disease loci in the mid-western Amish

Previous evidence has shown that Parkinson disease (PD) has a heritable component, but only a small proportion of the total genetic contribution to PD has been identified. Genetic heterogeneity complicates the verification of proposed PD genes and the identification of new PD susceptibility genes. Our approach to overcome the problem of heterogeneity is to study a population isolate, the mid-western Amish communities of Indiana and Ohio. We performed genome-wide association and linkage analyses on 798 individuals (31 with PD), who are part of a 4,998 member pedigree. Through these analyses, we identified a region on chromosome 5q31.3 that shows evidence of association (p value < 1 × 10^?4) and linkage (multipoint HLOD = 3.77). We also found further evidence of linkage on chromosomes 6 and 10 (multipoint HLOD 4.02 and 4.35 respectively). These data suggest that locus heterogeneity, even within the Amish, may be more extensive than previously appreciated.     

Integrated pharmacokinetic,pharmacodynamic and immunogenicity profiling of an anti-CCL21 monoclonal antibody in cynomolgus monkeys

QBP359 is an IgG1 human monoclonal antibody that binds with high affinity to human CCL21, a chemokine hypothesized to play a role in inflammatory disease conditions through activation of resident CCR7-expressing fibroblasts/myofibroblasts. The pharmacokinetics (PK) and pharmacodynamics (PD) of QBP359 in non-human primates were characterized through an integrated approach, combining PK, PD, immunogenicity, immunohistochemistry (IHC) and tissue profiling data from single- and multiple-dose experiments in cynomolgus monkeys. When compared with regular immunoglobulin typical kinetics, faster drug clearance was observed in serum following intravenous administration of 10 mg/kg and 50 mg/kg of QBP359. We have shown by means of PK/PD modeling that clearance of mAb-ligand complex is the most likely explanation for the rapid clearance of QBP359 in cynomolgus monkey. IHC and liquid chromatography mass spectrometry data suggested a high turnover and synthesis rate of CCL21 in tissues. Although lymphoid tissue was expected to accumulate drug due to the high levels of CCL21 present, bioavailability following subcutaneous administration in monkeys was 52%. In human disease states, where CCL21 expression is believed to be expressed at 10-fold higher concentrations compared with cynomolgus monkeys, the PK/PD model of QBP359 and its binding to CCL21 suggested that very large doses requiring frequent administration of mAb would be required to maintain suppression of CCL21 in the clinical setting. This highlights the difficulty in targeting soluble proteins with high synthesis rates.     

ER Stress Induced by Tunicamycin Triggers α-Synuclein Oligomerization,Dopaminergic Neurons Death and Locomotor Impairment: a New Model of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to the major clinical abnormalities that characterize this disease. Although PD’s etiology is unknown, α-synuclein aggregation plays a pivotal role in PD pathogenesis, which could be associated to some pathological processes such as oxidative stress, endoplasmic reticulum (ER) stress, impaired protein degradation, and mitochondrial dysfunction. Increasing experimental evidence indicates that ER stress is involved in PD, however most of the described results employed cultured cell lines and genetically modified animal models. In this study, we developed a new ER stress rat model employing the well-known ER stressor tunicamycin (Tm). To evaluate if ER stress was able to induce PD features, we performed an intranigral injection of Tm (0.1 μg/cerebral hemisphere) and animals (male Wistar rats) were analyzed 7 days post injection. The classical 6-OHDA neurotoxin model (1 μg/cerebral hemisphere) was used as an established positive control for PD. We show that Tm injection induced locomotor impairment, dopaminergic neurons death, and activation of astroglia. In addition, we observed an extensive α-synuclein oligomerization in SNpc of Tm-injected animals when compared with DMSO-injected controls. Finally, both Tm and 6-OHDA treated animals presented increased levels of ER stress markers. Taken together, these findings show for the first time that the ER stressor Tm recapitulates some of the phenotypic characteristics observed in rodent models of PD, reinforcing the concept that ER stress could be an important contributor to the pathophysiology of PD. Therefore, we propose the intranigral Tm injection as a new ER stress-based model for the study of PD in vivo.     

Alteration in Glutathione Content and Associated Enzyme Activities in the Synaptic Terminals but not in the Non-synaptic Mitochondria from the Frontal Cortex of Parkinson’s Disease Brains

Altered redox dynamics contribute to physiological aging and Parkinson’s disease (PD). This is reflected in the substantia nigra (SN) of PD patients as lowered antioxidant levels and elevated oxidative damage. Contrary to this observation, we previously reported that non-SN regions such as caudate nucleus and frontal cortex (FC) exhibited elevated antioxidants and lowered mitochondrial and oxidative damage indicating constitutive protective mechanisms in PD brains. To investigate whether the sub-cellular distribution of antioxidants could contribute to these protective effects, we examined the distribution of antioxidant/oxidant markers in the neuropil fractions [synaptosomes, non-synaptic mitochondria and cytosol] of FC from PD (n = 9) and controls (n = 8). In the control FC, all the antioxidant activities [Superoxide dismutase (SOD), glutathione (GSH), GSH peroxidase (GPx), GSH-S-transferase (GST)] except glutathione reductase (GR) were the highest in cytosol, but several fold lower in mitochondria and much lower in synaptosomes. However, FC synaptosomes from PD brains had significantly higher levels of GSH (p = 0.01) and related enzymes [GPx (p = 0.02), GR (p = 0.06), GST (p = 0.0001)] compared to controls. Conversely, mitochondria from the FC of PD cases displayed elevated SOD activity (p = 0.02) while the GSH and related enzymes were relatively unaltered. These changes in the neuropil fractions were associated with unchanged or lowered oxidative damage. Further, the mitochondrial content in the synaptosomes of both PD and control brains was ≥five-fold lower compared to the non-synaptic mitochondrial fraction. Altered distribution of oxidant/antioxidant markers in the neuropil fractions of the human brain during aging and PD has implications for (1) degenerative and protective mechanisms (2) distinct antioxidant mechanisms in synaptic terminals compared to other compartments.     

LRRK2 at the interface of autophagosomes,endosomes and lysosomes

Over the past 20 years, substantial progress has been made in identifying the underlying genetics of Parkinson’s disease (PD). Of the known genes, LRRK2 is a major genetic contributor to PD. However, the exact function of LRRK2 remains to be elucidated. In this review, we discuss how familial forms of PD have led us to hypothesize that alterations in endomembrane trafficking play a role in the pathobiology of PD. We will discuss the major observations that have been made to elucidate the role of LRRK2 in particular, including LRRK2 animal models and high-throughput proteomics approaches. Taken together, these studies strongly support a role of LRRK2 in vesicular dynamics. We also propose that targeting these pathways may not only be beneficial for developing therapeutics for LRRK2-driven PD, but also for other familial and sporadic cases.