Parkinson's Disease Pathway KEGG

http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38845

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic neurons in the substantia nigra. Mutations in alpha-synuclein, UCHL1 (ubiquitin carboxy-terminal hydrolase L1), parkin, DJ1 (a parkin-associated protein involved with oxidative stress), and PINK1 (a putative serine threonine kinase) are known to cause early-onset PD. Mutations or altered expression of these proteins contributes to PD pathogenesis through common mechanisms that result in proteasome dysfunction, mitochondrial impairment, and oxidative stress. Point mutations in alpha-synuclein and the recently described functional duplication of alpha-synuclein lead to excessive intracellular accumulation and protofibril formation. Decrease in the amount of soluble alpha-synuclein tends to increase free cytoplasmic dopamine and the formation of reactive oxygen species (ROS). Indeed, formation of protofibrils or aggregates and Lewy bodies (LBs) diminishes the availability of the physiological forms of alpha-synuclein, favoring an increase in TH (tyrosine hydroxylase) and DAT (dopamine transporter), but diminishes formation of vesicles and neuronal plasticity. Modification of parkin and UCHL1 are associated with the ubiquitin-proteasome system pathway and may increase proteotoxic stress. Mutations in parkin, DJ1, and PINK1 may alter mitochondrial activity, potentially impairing proteasomal function. Environmental toxins such as N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and rotenone can cause mitochondrial dysfunction and oxidative stress.

C38845

This pathway originally was KEGG_ID hsa05020.

Parkinson's Disease Pathway KEGG

Parkinson's Disease

hsa05012

Parkinson's Disease Pathway KEGG

Parkinsons_Disease_Pathway

Parkinson's Disease Pathway KEGG

Thesaurus:C38845

Parkinson's Disease Pathway KEGG

Functional Concept

C1521736

http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C39737