The Genetics of Parkinson's Disease

What are the genes that have been linked to Parkinson's disease?
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Terms in this set (22)
What are the genes that have been linked to Parkinson's disease?
LRRK2, SNCA, PARKIN, PINK1, DJ1
What is sporadic PD's greatest risk factor?
age
Which gene has the most significant contribution to sporadic PD?
SNCA
What is Genome Wide Association Studies' chief flaw?
They correlate common SNPs with disease phenotypes so will omit rarer variants that have potentially a higher odd for disease
What post-translational modification has been shown to reduce SNCA expression and how does this relate to patients with PD?
methylation. Methylation levels are reduced in the substantia nigra of sporadic PD patients, resulting in increased SNCA expression
SNCA
is a ubiquitous protein of unknown function, which was subsequently discovered to be the principle component of Lewy bodies
What results in development of PD in the 4th and 5th decades?
duplication of SNCA gene = 5th decade onset
triplication of SNCA gene = 4th decade onset
What is the key to the pathogenic properties of SNCA?
Transformation from its monomeric form to an aggregated beta sheet, with oligomeric and fibrilar intermediaries represents the source of toxicity
How does abnormally folded aggregated SNCA spread its structure to adjacent cells?
in a manner similar to prion disease
What are two suggested mechanisms of PD?
1) development of dopaminergic neurons via the Wnt pathway
2) aberrant brain iron accumulation by the DMT1 pathway
Which proteins are associated with the dynamic process of mitochondrial control and regulation and how do they function together as a unit?PINK1, PARKIN and DJ1. When damaged mitochondria are functionally impaired, PINK1 binds to the outer membrane. PARKIN is then recruited, designating the mitochondria for disposal by ubiquitination.Which genes produce a symmetrical loss of striatal signal?PARKIN and PINK1How does PARKIN-PD differ from other forms of PD?there is an absence of Lewy body pathologyWhat mutations are highly dependent on ethnicity?LRRK2 mutationsWhat mutations lead to Gaucher's disease?GBA mutationsTrue or False: Homozygous GBA carriers developed Parkinsonian symptomsFalse. HeterozygousWhat results from the inhibition of knowckdown of GBA?accumulation of SNCA in cell lines expression pathogenic PD mutationsWhat happens to GBA when SNCA is overexpressed?leads to reduced GBA activityWhat is ambroxol and what happens when disease carrying fibroblasts and neuroblastoma cells are treated with it?Ambroxol is a pH dependent mixed type inhibitor of GBA. It appears to restore GBA activity in GBA mutant cell lines and reduce SNCA expression in SNCA linesWhat may be a risk factor for cognitive decline in sporadic PD?MAPT H1/H1 haplotypeHow is parkinsonism inherited?maternally inherited mutations of mtDNA across all the mitochondria in the organismHIV patients with prolonged exposure to what appear to be developing parkinsonism at a comparatively young age?nucleoside reverse transcriptase inhibitors