Novel compounds for the modulation of mTOR and autophagy to treat neurodegenerative diseases |
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| Institution: | 1. Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico;2. Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Mexico City, Mexico;1. Department of Pathology, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China;2. Institute of Neuroscience, Yuanjiagang Yixueyuan Road NO. 1, Chongqing 400016, China;3. Foreign languages Department, Chongqing Medical University, Chongqing 400016, China;1. Lingnan Normal University, Zhanjiang 524048, PR China;2. Hainan Medical University, Haikou, 571199, PR China;3. Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, and The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou 510120, PR China;4. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China;5. The First Affiliated Hospital of Henan University of TCM，450000，PR China;1. Department of Physiology, Basic Medical College of Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, China;2. Department of Nephrology, Taian City Central Hospital, Taian, 271000, China;3. Postdoctoral Workstation, Taian City Central Hospital, Taian, 271000, China;4. Life Science Research Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, China;5. Department of Electrocardiogram, Taian Traditional Chinese Medicine Hospital, Taian, 271000, China;1. Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea;2. Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;3. Natural Medicine Center, Korea Institute of Science and Technology, Gangneung 210-340, Republic of Korea;4. School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea;5. Department of Neurology, Gangnung Asan Hospital, Biomedical Research Center, Gangneung, Republic of Korea;6. Department of Neurology, Hanyang University College of Medicine, Seoul, Republic of Korea |
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| Abstract: | Most neurodegenerative diseases show a disruption of autophagic function and display abnormal accumulation of toxic protein aggregates that promotes cellular stress and death. Therefore, induction of autophagy has been proposed as a reasonable strategy to help neurons clear abnormal protein aggregates and survive. The kinase mammalian target of rapamycin (mTOR) is a major regulator of the autophagic process and is regulated by starvation, growth factors, and cellular stressors. The phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway, which promotes cellular survival, is the main modulator upstream of mTOR, and alterations in this pathway are common in neurodegenerative diseases, e.g. Alzheimer’s disease (AD) and Parkinson’s disease (PD). In the present work we revised mammalian target of rapamycin complex 1 (mTORC1) pathway and mTORC2 as a complementary an important element in mTORC1 signaling. In addition, we revised the extracellular signal regulated kinase (ERK) pathway, which has become relevant in the regulation of the autophagic process and cellular survival through mTORC2 signaling. Finally, we summarize novel compounds that promote autophagy and neuronal protection in the last five years. |
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| Keywords: | Mammalian target of rapamycin complex Autophagy Parkinson's disease Alzheimer's disease Neurodegeneration Phosphatidylinositol-3-kinase Mitogen activated protein kinases Beclin-1 Apelin Cubeben Curcumin |
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