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Content archived on 2024-05-29

Parkinson's disease and mitochondria dysfunction

Objective

SUMMARY OF PROPOSED ACTIVITY Parkinsons Disease (PD) is a common progressive neurodegenerative disorder, characterized by postural instability, rigidity, tremor and bradykinesia. The pathological hallmark of PD is the loss of dopaminergic neurons in the sub stantia nigra. One important feature of PD is the presence of cytoplasmic inclusions of fibrillar, misfolded proteins, termed Lewy bodies, in affected brain areas.

The etiology of PD remains unknown, although clinical and experimental evidence implicate t he involvement of mitochondrial dysfunction and oxidative stress. Rare hereditary forms of PD have provided insights into the molecular pathways of this disorder. Mutations in at least five genes have been linked to PD including a-synuclein (PARK1), parkin (PARK2), DJ-1 (PARK7), LRRK2 (PARK8) and PINK1 (PARK6). New data revealed that at least ten different mutations in the gene encoding for PINK1 are associated with recessive forms of early onset PD. The PINK1 gene is located on chromosome 1p35-36 and encodes a 581 amino acid protein of unknown function, with N-terminal mitochondria targeting peptide and a putative serine/tyrosine kinase domain.

The targeting of PINK1 to the mitochondria suggests that this protein may phosphorylate a mitochondrial target(s) that might play a role in protecting cells from loss of mitochondrial membrane potential and possibly oxidative stress. We will analyse the effect of PINK1 mutations on mitochondrial dynamics and function, and create a mouse model for PD using the novel approach of recombinase-mediated DNA cassette exchange (RMCE) that allows the evaluation of both loss and gain of function in mice.

Call for proposal

FP6-2005-MOBILITY-5
See other projects for this call

Coordinator

FLANDERS INTERUNIVERSITARY INSTITUTE FOR BIOTECHNOLOGY VZW
EU contribution
No data
Total cost
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