Article

Involvement of PTPN5, the gene encoding the striatal-enriched protein tyrosine phosphatase, in schizophrenia and cognition.

Department of Psychiatry, Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Psychiatric genetics (impact factor: 2.33). 05/2012; 22(4):168-76. DOI:10.1097/YPG.0b013e3283518586 pp.168-76
Source: PubMed

ABSTRACT Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific member of the protein tyrosine phosphatase (PTP) family that has been implicated in learning and memory. In this study, we examined the association of the protein tyrosine phosphatase non-receptor 5 (PTPN5) gene, which encodes for STEP, with both schizophrenia and cognitive functioning in the Israeli Jewish population.
A schizophrenia (SZ) case-control study of 868 participants was carried out (286 patients and 582 controls). Eleven PTPN5 tagging single-nucleotide polymorphisms (SNPs) were selected and single markers and haplotype association analyses were carried out. A cognitive variability study included 437 healthy women who completed a computerized cognitive battery. We performed univariate associations between the SNPs and cognitive performance. The possible functional role of these variants was examined by studying their association with gene expression levels in the brain.
In the SZ study, we found a nominal association in the whole sample between rs4075664 and SZ. Male patients with SZ showed a more significant association for three SNPs (rs4075664, rs2278732, and rs4757710). Haplotypes of the studied SNPs were associated with SZ both in the overall sample and within the male subsample. Expression analysis provided some support for the effects of the associated SNPs on PTPN5 expression level. The cognitive variability study showed positive associations between PTPN5 SNPs and different cognitive subtests. Principal component analysis showed an 'attention index' neurocognitive component that was associated with two SNP pairs (rs10832983 × rs10766504 and rs7932938 × rs4757718).
The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contribute to aspects of the neuropathology of SZ.

0 0
 · 
0 Bookmarks
 · 
32 Views
  • Source
    Article: Cognitive Enhancers (Nootropics). Part 2: Drugs Interacting with Enzymes.
    Wolfgang Froestl, Andreas Muhs, Andrea Pfeifer
    [show abstract] [hide abstract]
    ABSTRACT: Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 19 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease modifying drugs meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. This review covers the evolution of research in this field over the last 25 years.
    Journal of Alzheimer's disease: JAD 10/2012; · 3.74 Impact Factor
  • Source
    Dataset: Froestl 2013 Part2
    Wolfgang Froestl, Andrea Pfeifer, Andreas Muhs
  • Source
    Dataset: Froestl 2013 Part2
    Andrea Pfeifer, Andreas Muhs, Wolfgang Froestl

Show more

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

'attention index' neurocognitive component
 
437 healthy women
 
associated SNPs
 
brain-specific member
 
computerized cognitive battery
 
different cognitive subtests
 
gene expression levels
 
male subsample
 
nominal association
 
normal cognitive
 
possible functional role
 
protein tyrosine phosphatase
 
protein tyrosine phosphatase non-receptor 5
 
PTPN5 expression level
 
PTPN5 SNPs
 
PTPN5 tagging single-nucleotide polymorphisms
 
significant association
 
Striatal-enriched protein tyrosine phosphatase
 
studied SNPs
 
whole sample
 

Ilana Pelov