Data di Pubblicazione:
2005
Abstract:
Senile plaques and neurofibrillary tangles (NFT) are the prominent lesions in the brain of Alzheimer’s disease (AD) patients. NFT are mainly
composed of an abnormally phosphorylated form of tau protein, which has lost its function to bind microtubules and promote their assembly.
Tau hyperphosphorylation critically decreases tau function and precedes neurodegeneration. The majority of tau phosphorylation sites are
Ser/Thr-Pro motifs, which are known to exist in two distinct cis and trans conformations. The prolyl isomerase Pin1 catalyses the conversion
of those conformations. Pin1 binds to tau specifically at the Thr231-Pro site and restores tau function, either by inducing conformational
changes or facilitating dephosphorylation. It has been shown that Pin1 expression levels inversely correlate with the predicted vulnerability
of different brain areas to neurodegeneration and soluble Pin1 is depleted in neurons from AD brains; furthermore, Pin1 knock-out mice
develop signs and symptoms of tau-related pathologies late in life. It seems that Pin1 plays an important role in maintaining tau function,
thereby preserving neuronal homeostasis and preventing age-dependent neurodegeneration. DNA sequence variations in Pin1 gene may affect
its expression level or function and influence the individual risk for developing AD. We screened by denaturing high performance liquid
chromatography the genomic DNA of 120 AD subjects and 134 age-matched controls and we found very few and rare sequence variations
in the promoter region and in exons 2 and 3. We conclude that Pin1 is a very well conserved gene, whose rare nucleotide variations have no
effect on the individual genetic risk for AD.
composed of an abnormally phosphorylated form of tau protein, which has lost its function to bind microtubules and promote their assembly.
Tau hyperphosphorylation critically decreases tau function and precedes neurodegeneration. The majority of tau phosphorylation sites are
Ser/Thr-Pro motifs, which are known to exist in two distinct cis and trans conformations. The prolyl isomerase Pin1 catalyses the conversion
of those conformations. Pin1 binds to tau specifically at the Thr231-Pro site and restores tau function, either by inducing conformational
changes or facilitating dephosphorylation. It has been shown that Pin1 expression levels inversely correlate with the predicted vulnerability
of different brain areas to neurodegeneration and soluble Pin1 is depleted in neurons from AD brains; furthermore, Pin1 knock-out mice
develop signs and symptoms of tau-related pathologies late in life. It seems that Pin1 plays an important role in maintaining tau function,
thereby preserving neuronal homeostasis and preventing age-dependent neurodegeneration. DNA sequence variations in Pin1 gene may affect
its expression level or function and influence the individual risk for developing AD. We screened by denaturing high performance liquid
chromatography the genomic DNA of 120 AD subjects and 134 age-matched controls and we found very few and rare sequence variations
in the promoter region and in exons 2 and 3. We conclude that Pin1 is a very well conserved gene, whose rare nucleotide variations have no
effect on the individual genetic risk for AD.
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
Poli, M; Gatta, Lb; Dominici, R; Lovati, C; Mariani, C; Albertini, Alberto; Finazzi, Dario
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