Synaptojanin 1 mutation in Parkinson's disease brings further insight into the neuropathological mechanisms.

ABSTRACT: Synaptojanin 1 (SYNJ1) is a phosphoinositide phosphatase highly expressed in nerve terminals. Its two phosphatase domains dephosphorylate phosphoinositides present in membranes, while its proline-rich domain directs protein-protein interactions with synaptic components, leading to efficient recycling of synaptic vesicles in neurons. Triplication of SYNJ1 in Down's syndrome is responsible for higher level of phosphoinositides, enlarged endosomes, and learning deficits. SYNJ1 downregulation in Alzheimer's disease models is protective towards amyloid-beta peptide (Aβ) toxicity. One missense mutation in one of SYNJ1 functional domains was recently incriminated in an autosomal recessive form of early-onset Parkinson's disease (PD). In the third decade of life, these patients develop progressive

SUBMITTER: Drouet V 

PROVIDER: S-EPMC4181773 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature