Examining the Toxicity of α-Synuclein in Neurodegenerative Disorders

SIMPLE SUMMARY: Neurodegenerative disorders are complex disorders that display a variety of clinical manifestations. The second-most common neurodegenerative disorder is Parkinson’s disease, and the leading pathological protein of the disorder is considered to be α-synuclein. Nonetheless, α-synuclein accumulation also seems to result in multiple system atrophy and dementia with Lewy bodies. In order to obtain a more proficient understanding in the pathological progression of these synucleinopathies, it is crucial to observe the post-translational modifications of α-synuclein and the conformations of α-synuclein, as well as its role in the dysfunction of cellular pathways. ABSTRACT: α-synuclein is considered the main pathological protein in a variety of neurodegenerative disorders, such as Parkinson’s disease, multiple system atrophy, and dementia with Lewy bodies. As of now, numerous studies have been aimed at examining the post-translational modifications of α-synuclein to determine their effects on α-synuclein aggregation, propagation, and oligomerization, as well as the potential cellular pathway dysfunctions caused by α-synuclein, to determine the role of the protein in disease progression. Furthermore, α-synuclein also appears to contribute to the fibrilization of tau and amyloid beta, which are crucial proteins in Alzheimer’s disease, advocating for α-synuclein’s preeminent role in neurodegeneration. Due to this, investigating the mechanisms of toxicity of α-synuclein in neurodegeneration may lead to a more proficient understanding of the timeline progression in neurodegenerative synucleinopathies and could thereby lead to the development of potent targeted therapies.