Alpha-Synuclein Aggregation in Parkinson's Disease

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

doi:10.3389/fmed.2021.736978

Alpha-Synuclein Aggregation in Parkinson's Disease

Front Med (Lausanne). 2021 Oct 18:8:736978. doi: 10.3389/fmed.2021.736978. eCollection 2021.

Authors

E Srinivasan^{1

2}, G Chandrasekhar¹, P Chandrasekar¹, K Anbarasu², A S Vickram³, Rohini Karunakaran⁴, R Rajasekaran¹, P S Srikumar⁵

Affiliations

¹ Bioinformatics Lab, Department of Biotechnology, School of Bio Sciences and Technology, Vellore Institute of Technology (Deemed to be University), Vellore, India.
² Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, India.
³ Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, India.
⁴ Unit of Biochemistry, Faculty of Medicine, AIMST University, Bedong, Malaysia.
⁵ Unit of Psychiatry, Faculty of Medicine, AIMST University, Bedong, Malaysia.

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.

Keywords: Parkinson's; alpha-synuclein; genes; mutation; protein aggregation.

Publication types

Review