Challenges and complexities of alpha-synuclein toxicity: new postulates in unfolding the mystery associated with Parkinson's disease |
| |
Authors: | Hegde Muralidhar L Jagannatha Rao K S |
| |
Affiliation: | Department of Biochemistry and Nutrition, Central Food Technological Research Institute, 570013, Mysore, India. |
| |
Abstract: | The discovery of two missense mutations in alpha-synuclein gene and the identification of the alpha-synuclein as the major component of Lewy bodies and Lewy neurites have imparted a new direction in understanding Parkinson's disease. Now that alpha-synuclein has been implicated in several neurodegenerative disorders makes it increasingly clear that aggregation of alpha-synuclein is a hallmark feature in neurodegeneration. Although little has been learned about its normal function, alpha-synuclein appears to be associated with membrane phospholipids and may therefore participate in a number of cell signaling pathways. Here, we review the localization, structure, and function of alpha-synuclein and provide a new hypothesis on, (a) the disruption in the membrane binding ability of synuclein which may be the major culprit leading to the alpha-synuclein aggregation and (b) the complexity associated with nuclear localization of alpha-synuclein and its possible binding property to DNA. Further, we postulated the three possible mechanisms of synuclein induced neuronal degeneration in Parkinson's disease. |
| |
Keywords: | α-Synuclein Parkinson’s disease Neurodegeneration Protein aggregation Membrane binding Neuronal plasticity |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|