TY - JOUR
T1 - Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathies
AU - Ramakrishnan, Pankajavalli
AU - Dickson, Dennis W.
AU - Davies, Peter
N1 - Funding Information:
We thank Chris Conrad for his help with cloning human Pin1 into a prokaryotic expression vector. This study was supported by the Medical Scientist Training Program (M.S.T.P.) training Grant T32GM07288 to Pankajavalli Ramakrishnan and by the National Institute of Mental Health (N.I.M.H.) Grant 38623 to Dr. Peter Davies.
PY - 2003/11
Y1 - 2003/11
N2 - Pin1, a peptidyl-prolyl isomerase binds to mitotic serine or threonine phosphoproteins. In Alzheimer's disease (AD) evidence points to the reactivation of mitosis in vulnerable neurons. Tangles composed of hyperphosphorylated tau contain phosphorylated Thr231 (pThr 231 tau), which occurs to a greater extent in the AD brain than in the normal brain, and Pin1 has been shown to bind pThr231 tau. Here, Pin1 distribution in AD, and its colocalization with pThr231 tau in AD, FTDP-17 (P301L), Pick's disease (PiD), and PSP was investigated using TG-3, a monoclonal antibody to conformationally altered pThr231 tau. The Pin1 antibody A-20 detected granular Pin1 staining in AD brains, but not in normal brains. A-20 immunoreactive granules colocalized with TG-3-stained granules but not with TG-3-stained pretangles, tangles, or Pick bodies in AD, PiD, and FTDP-17 (P301L). Pin1 granules were sparse in PSP, and rarely did A-20 colocalize with TG-3. The appearance of Pin1 granules in the early stages of AD, PiD, and FTDP-17 (P301L) implicates Pin1 in their pathogenesis but not in PSP.
AB - Pin1, a peptidyl-prolyl isomerase binds to mitotic serine or threonine phosphoproteins. In Alzheimer's disease (AD) evidence points to the reactivation of mitosis in vulnerable neurons. Tangles composed of hyperphosphorylated tau contain phosphorylated Thr231 (pThr 231 tau), which occurs to a greater extent in the AD brain than in the normal brain, and Pin1 has been shown to bind pThr231 tau. Here, Pin1 distribution in AD, and its colocalization with pThr231 tau in AD, FTDP-17 (P301L), Pick's disease (PiD), and PSP was investigated using TG-3, a monoclonal antibody to conformationally altered pThr231 tau. The Pin1 antibody A-20 detected granular Pin1 staining in AD brains, but not in normal brains. A-20 immunoreactive granules colocalized with TG-3-stained granules but not with TG-3-stained pretangles, tangles, or Pick bodies in AD, PiD, and FTDP-17 (P301L). Pin1 granules were sparse in PSP, and rarely did A-20 colocalize with TG-3. The appearance of Pin1 granules in the early stages of AD, PiD, and FTDP-17 (P301L) implicates Pin1 in their pathogenesis but not in PSP.
KW - Alzheimer's disease
KW - Neurodegeneration
KW - Pin1
KW - Tau
KW - Tauopathies
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U2 - 10.1016/S0969-9961(03)00109-8
DO - 10.1016/S0969-9961(03)00109-8
M3 - Article
C2 - 14572447
AN - SCOPUS:0142157635
SN - 0969-9961
VL - 14
SP - 251
EP - 264
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -