Parkinsons Disease: Genetics and Beyond

Abstract

Parkinson's disease (PD) is characterized clinically by resting tremor, rigidity, bradykinesia and postural instability due to progressive and selective loss of dopamine neurons in the ventral substantia nigra, with the presence of ubiquitinated protein deposits called Lewy bodies in the neurons. The pathoetiology of cell death in PD is incompletely understood and evidence implicates impaired mitochondrial complex I function, altered intracellular redox state, activation of proapoptotic factors and dysfunction of ubiquitinproteasome pathway. Now it is believed that genetic aberration, an environmental toxin or combination of both leads to a cascade of events culminating in the destruction of myelinated brainstem catecholaminergic neurons. Also the role of production of significant levels of abnormal proteins, which may misfold, aggregate and interfere with intracellular processes causing cytotoxicity has recently been hypothesized. In this article, the diverse pieces of evidence that have linked the various factors responsible for the pathophysiology of PD are reviewed with special emphasis to various candidate genes and proteins. Furthermore, the present therapeutic strategies and futuristic approaches for the pharmacotherapy of PD are critically discussed.

Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element

“…Patients refer to slowness in performing their daily activities. Rigidity of muscles on passive movement, including joints, is also a characteristic of PD [ 3 ].…”

Synergistic action of propolis with levodopa in the management of Parkinsonism in Drosophila melanogaster

“…These symptoms are both in humans [2,3] and in animal models of PD [4,5]. PTEN-induced putative kinase 1 (PINK1) is responsible for the maintenance of mitochondria structure and function [6][7][8]. Loss of PINK1 gene in Drosophila culminates in a phenotype expressing Parkinsonism, with mitochondrial destruction occurring before muscle degeneration, as well as the destruction of dopaminergic neurons [3].…”

Selection of Cells for Parkinson's Disease Cell-Therapy

“…The aetiology are unknown, however many different factors can be counted like, ageing, external assaults, toxicity or may be genetic abnormalities [30].…”