Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-9-6
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0304-3940
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
389
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
66-70
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16095818-Aged, pubmed-meshheading:16095818-Aged, 80 and over, pubmed-meshheading:16095818-Alzheimer Disease, pubmed-meshheading:16095818-Base Sequence, pubmed-meshheading:16095818-Brain, pubmed-meshheading:16095818-Brain Chemistry, pubmed-meshheading:16095818-Conserved Sequence, pubmed-meshheading:16095818-DNA Mutational Analysis, pubmed-meshheading:16095818-Female, pubmed-meshheading:16095818-Gene Expression Regulation, Enzymologic, pubmed-meshheading:16095818-Genetic Predisposition to Disease, pubmed-meshheading:16095818-Genetic Testing, pubmed-meshheading:16095818-Genetic Variation, pubmed-meshheading:16095818-Genotype, pubmed-meshheading:16095818-Humans, pubmed-meshheading:16095818-Isoenzymes, pubmed-meshheading:16095818-Male, pubmed-meshheading:16095818-Middle Aged, pubmed-meshheading:16095818-Mutation, pubmed-meshheading:16095818-Neurofibrillary Tangles, pubmed-meshheading:16095818-Peptidylprolyl Isomerase, pubmed-meshheading:16095818-Phosphorylation, pubmed-meshheading:16095818-tau Proteins
pubmed:year
2005
pubmed:articleTitle
DNA sequence variations in the prolyl isomerase Pin1 gene and Alzheimer's disease.
pubmed:affiliation
Section of Biochemistry, Faculty of Medicine, University of Brescia, Viale Europe 11, 25123 Brescia, Italy.
pubmed:publicationType
Journal Article