Premium
O2–01–07: Influence of dopaminergic neurotransmission in AD pathophysiology
Author(s) -
Lyckman Alvin
Publication year - 2007
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2007.04.050
Subject(s) - dopaminergic , neurodegeneration , neuroscience , dopamine , neuropathology , oxidative stress , entorhinal cortex , neurotransmission , medicine , endocrinology , biology , hippocampus , disease , receptor
Methods: Abnormally hyperphosphorylated tau was isolated from AD brain cytosol (AD P-tau), and its ability to inhibit microtubule assembly and self-assembly into filaments was studied before and after dephosphorylation with protein phosphatase-2A (PP-2A), and after rephosphorylation by several combinations of tau kinases. Results: We found that dephosphorylation of AD P-tau by PP-2A converts it into a normal-like protein and on rephosphorylation by PKA, cdk5 and GSK-3 or cdk5 or cdk5 plus GSK-3 , converts it back into an AD-type pathological protein. Investigation of site-specific phosphorylation revealed that phosphorylation of tau at Thr231 and Ser262 plays a pivotal role in its conversion into AD-like pathological protein. Conclusions: More than one etiopathogenic mechanism might be involved in AD-type neurofibrillary degeneration, and inhibition of more than one tau kinase might be required to inhibit neurofibrillary degeneration.