Alpha-Synuclein Aggregation in Parkinson's Disease.

E Srinivasan,K Anbarasu,P Chandrasekar,A S Vickram,G Chandrasekhar,P S Srikumar,R Rajasekaran,Rohini Karunakaran

doi:10.3389/fmed.2021.736978

Abstract

Parkinson's disease (PD), a neurodegenerative disorder characterized by distinct aging-independent loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) region urging toward neuronal loss. Over the decade, various key findings from clinical perspective to molecular pathogenesis have aided in understanding the genetics with assorted genes related with PD. Subsequently, several pathways have been incriminated in the pathogenesis of PD, involving mitochondrial dysfunction, protein aggregation, and misfolding. On the other hand, the sporadic form of PD cases is found with no genetic linkage, which still remain an unanswered question? The exertion in ascertaining vulnerability factors in PD considering the genetic factors are to be further dissevered in the forthcoming decades with advancement in research studies. One of the major proponents behind the prognosis of PD is the pathogenic transmutation of aberrant alpha-synuclein protein into amyloid fibrillar structures, which actuates neurodegeneration. Alpha-synuclein, transcribed by SNCA gene is a neuroprotein found predominantly in brain. It is implicated in the modulation of synaptic vesicle transport and eventual release of neurotransmitters. Due to genetic mutations and other elusive factors, the alpha-synuclein misfolds into its amyloid form. Therefore, this review aims in briefing the molecular understanding of the alpha-synuclein associated with PD.

Highlights

Parkinson’s disease (PD) is the second most common neurodegenerative disorder that falls under the category of synucleinopathy [1]
This review offers an analytical assessment of the literature designating the possible role of the genes involved in causing PD
The present review covers a broad range of information on the disease-causing gene AS related to PD disorder

Summary

Introduction

Parkinson’s disease (PD) is the second most common neurodegenerative disorder that falls under the category of synucleinopathy [1]. PD is characterized by distinct aging-independent loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) region and the decrease in dopamine levels [2]. PD leads to the loss of terminal ends of striatum, which occurs before the neuronal loss in SNpc and; it seems to be more significant in disease pathogenesis [3]. About 95% of PD cases are sporadic with no genetic linkage. PD has its mean age of onset at 55 years with increased incidences with aging [1]. PD is the most common disorder in a range of disorders classified as Parkinsonism characterized by dopamine deficiency and striatal damage

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Conclusion