Chaperone proteins as ameliorators of alpha-synuclein-induced synaptic pathologies: Insights into Parkinson's disease
Banks, Susan M. L.
Medeiros, Audrey T.
Lafer, Eileen M.
Morgan, Jennifer R.
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α-Synuclein accumulation causes synaptic vesicle trafficking defects and may underlie neurodegenerative disorders: Neurodegenerative disorders, such as Parkinson’s disease (PD) and other synucleinopathies, impact the lives of millions of patients and their caregivers. Synucleinopathies include PD, dementia with Lewy Bodies (DLB), multiple system atrophy, and several Alzheimer’s Disease variants. They are clinically characterized by intracellular inclusions called Lewy Bodies, which are rich in atypical aggregates of the protein α-synuclein. While dopaminergic neurons in the substantia nigra are particularly susceptible to α-synuclein-induced aggregation and neurodegeneration, glutamatergic neurons in other brain regions (e.g. cortex) are also frequently affected in PD and other synucleinopathies (Schulz-Schaeffer 2010). Several point mutations in the α-synuclein gene (SNCA), as well as duplication/triplication of SNCA, are linked to familial Parkinson’s disease. In animal models, these genetic alterations lead to overexpression and aberrant accumulation of α-synuclein within neurons, and eventually to neurodegeneration. Interestingly, in both animal models and human patients, α-synuclein aggregation often occurs at neuronal synapses and within axons prior to the appearance of larger aggregates (i.e. Lewy bodies) and other signs of neurodegeneration (Schulz-Schaeffer 2010; Volpicelli-Daley et al., 2011). The level of synaptic aggregation of α-synuclein is highly correlated with greater cognitive deficits in PD and DLB patients (Schulz-Schaeffer 2010). Thus, it is essential to understand how excess α-synuclein impacts synapses, as this may represent an early stage in the neurodegenerative disease progression and thus a viable target for therapeutic intervention, particularly with respect to cognitive impairment.
© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Banks, S. M. L., Medeiros, A. T., Sousa, R., Lafer, E. M., & Morgan, J. R. Chaperone proteins as ameliorators of alpha-synuclein-induced synaptic pathologies: Insights into Parkinson's disease. Neural Regeneration Research, 16(6), (2021): 1198-1199, doi:10.4103/1673-5374.300431.
Suggested CitationBanks, S. M. L., Medeiros, A. T., Sousa, R., Lafer, E. M., & Morgan, J. R. (2021). Chaperone proteins as ameliorators of alpha-synuclein-induced synaptic pathologies: Insights into Parkinson's disease. Neural Regeneration Research, 16(6), 1198-1199.
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