Title:Ignored Avenues in Alpha-Synuclein Associated Proteopathy
VOLUME: 13 ISSUE: 7
Author(s):Rimpy K. Chowhan, Shruti Mittal, Tanveer A. Dar, Mohammad A. Kamal and Laishram R. Singh
Affiliation:Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
Keywords:Alpha-synuclein, cancer, cardiovascular disorders, neurodegeneration, Parkinson’s disease, proteiopathy.
Abstract:Alpha-Synuclein (αSyn) is a 14 kDa pre-synaptic protein predominantly expressed in various regions of brain
comprising neocortex, hippocampus, striatum, thalamus and cerebellum. αSyn aggregates have special neuropathologic
relevance for comprehending Parkinson’s disease (PD) and other synucleopathies due to the presence of αSyn aggregates
in brain of patients suffering from these diseases. Direct relationship between PD and various single nuclear
polymorphisms of αSyn further displays an inherent significance of mutated αSyn in increasing the risk for developing
PD. So far, various theories have been emerged to explain αSyn mediated neuronal cell toxicity seen in patients with PD,
including interaction of αSyn aggregates with biomolecules, vesicle dystrafficking, augmented oxidative stress,
mitochondrial dysfunction, and disruption of synaptic function. Despite the advances in understanding of PD
pathophysiology, current available treatments are still aiming at giving symptomatic relief. Lately, PD vaccines against
αSyn aggregates are also being considered. However, various other avenues for e.g. post-translational and conformational
modifications of αSyn, effect of cellular small molecules such as polyamines and osmolytes on αSyn aggregation, still
remain unexplored and we believe that therapeutics directed at these ignored targets will surface as a successful
combinational therapy for PD. Additionally, understanding mechanisms behind the interplay between PD and other health
conditions, such as Gaucher’s disease, Cardiovascular disorders, Hypertension, Homocystinuria, Type-II Diabetes, and
Cancer are also speculated to provide great insight for novel therapeutic interventions. In the current review, we have
precisely discussed all these ignored avenues with their possible clinical implications. Link between PD and other
associated diseases has also been extensively reviewed.
