Last updated: August 28, 2019
Topic: HealthDisease
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disease (PD) is the second most common neurodegenerative disease after
Alzheimer’s disease. The disease prevalence increases with increasing age. The
disease is mainly characterized by the motor symptoms – Tremor, rigidity, bradykinesia and postural instability. Some PD patients also harbor non-motor symptoms
including autonomic dysfunction, cognitive impairments, sleep disturbance and olfactory dysfunction. Neurodegeneration
in the substantia nigra pars compacta
and the deposition of Lewy body in
the surviving neurons (Figure1) are two major hallmarks of PD. The
molecular mechanism causing dopaminergic cell death in substantia nigra is very
complex. The postmortemed PD brains revealed increased oxidative damage of
lipids and proteins. It is evident that the dysfunctions of cellular
ubiquitin-proteosomal system (UPS) and mitochondrial system lead to
dopaminergic cell loss in substantia nigra of the PD patients. It is also
speculated that the axonal transport system can play a role in the pathogenesis
of PD Millecamps et al., 2013.
PD is a multifactorial disease, where genetic as well as
environmental factors play significant role. PD
is mostly sporadic. Only 10-15% of the cases are familial. So far, 23 loci
(PARK 1-23) have been identified for PD either by linkage analysis (PARK1-15)
or by genome wide association studies (GWAS, PARK16-18) (Table 1). A total of
18 genes have been implicated of which four genes, ?-synuclein (SNCA), Leucine-rich repeat kinase 2 (LRRK2),
Ubiquitin carboxy-terminal hydrolase L-1 (UCHL-1), GRB10-interacting GYF
protein 2 (GIGYF2) (Trinucleotide
repeat-containing gene 15 protein, TNRC15) inherit in the autosomal
dominant trait and 5 genes, Parkin, DJ-1, PTEN induced putative kinase1
(PINK1), ATPase type 13A2 (ATP13A2) inherit in autosomal recessive trait.
Some of the common variants of these familial genes have also been identified
as susceptible locus for the sporadic cases.Our
laboratory has been studying the molecular genetics of PD pathogenesis.. We
have reported  mutation profile of Parkin Biswas et al., 2006 and 2007, PINK1
Biswas et al., 2010, DJ-1 Sadhukhanet al., 2012, LRRK-2
Sadhukhanet al., 2012 and
association of common variants of MAPT
Das et al., 2009, GST Biswas
et al., 2012, GSK3? and CDK5R1 Das et al., 2012, etc. in PD.