TY - JOUR
T1 - Molecular dissection of the paired helical filament
AU - Goedert, M.
AU - Spillantini, M. G.
AU - Jakes, R.
AU - Crowtherp, R. A.
AU - Vanmechelen, E.
AU - Probst, A.
AU - Götz, J.
AU - Bürki, K.
AU - Cohen, P.
PY - 1995
Y1 - 1995
N2 - Abundant neurofibrillary tangles, neuropil threads and plaque neurites constitute the neurofibrillary pathology of Alzheimer's disease. They form in the nerve cells that undergo degeneration in the disease where their regional distribution correlates with the degree of dementia. Each lesion contains the paired helical filament (PHF) as its major fibrous component. Recent work has shown that PHFs are composed of the microtubule-associated protein tau in a hyperphosphorylated state. PHF-tau is hyperphosphorylated on six adult brain tau isoforms. As a consequence, tau is unable to bind to microtubules and is believed to self-assemble into the PHF. Current evidence suggests that protein kinases or protein phosphatases with a specificity for serine/threonine-proline residues play an important role in the hyperphosphorylation of tau. Candidate protein kinases include mitogen-activated protein kinase, glycogen synthase kinase-3 and cyclin-dependent kinase 5, whereas the trimeric form of protein phosphatase 2A is a candidate phosphatase.
AB - Abundant neurofibrillary tangles, neuropil threads and plaque neurites constitute the neurofibrillary pathology of Alzheimer's disease. They form in the nerve cells that undergo degeneration in the disease where their regional distribution correlates with the degree of dementia. Each lesion contains the paired helical filament (PHF) as its major fibrous component. Recent work has shown that PHFs are composed of the microtubule-associated protein tau in a hyperphosphorylated state. PHF-tau is hyperphosphorylated on six adult brain tau isoforms. As a consequence, tau is unable to bind to microtubules and is believed to self-assemble into the PHF. Current evidence suggests that protein kinases or protein phosphatases with a specificity for serine/threonine-proline residues play an important role in the hyperphosphorylation of tau. Candidate protein kinases include mitogen-activated protein kinase, glycogen synthase kinase-3 and cyclin-dependent kinase 5, whereas the trimeric form of protein phosphatase 2A is a candidate phosphatase.
KW - Hyperphosphorylation
KW - Neurofibrillary lesions
KW - Paired helical filaments
KW - Tau protein
UR - http://www.scopus.com/inward/record.url?scp=0029031214&partnerID=8YFLogxK
U2 - 10.1016/0197-4580(95)00017-9
DO - 10.1016/0197-4580(95)00017-9
M3 - Article
C2 - 7566342
AN - SCOPUS:0029031214
VL - 16
SP - 325
EP - 334
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 3
ER -