ROLE OF PINCH IN ABERRANT TAU PHOSPHORYLATION IN HIV CNS DISEASE
type: CreativeWork
description: Aged HIV-positive (HIV+) individuals represent a large proportion of the HIV population as life spans are extended significantly by successful antiretroviral therapy. Increased age with HIV infection brings a unique set of central nervous system (CNS) complications including more rapid onset and progression of age-related diseases, loss of protein quality control and accumulation of aberrant proteins, such as hyperphosphorylated Tau (hpTau). In this context, we have discovered a new signaling connection between age-related neurodegeneration and HIV involving the PINCH protein. Particularly interesting new cysteine histidine-rich protein (PINCH), an adaptor protein in neuronal cells is involved in cytoskeletal organization, cell migration and cell survival. While some of the pathophysiological aspects of the PINCH-signaling cascade in tauopathy are largely conserved among neurodegenerative diseases such as Alzheimer’s disease, HIV and others, the presence of the HIV protein Tat impacts specific key points in the PINCH pathway that exacerbate CNS cell dysfunction. In virus-infected cells, Tat regulates viral replication. Even though neurons are not permissive to viral infection, the Tat protein can enter all cell types. Our studies show that Tat interferes with key PINCH signaling partners in neurons. PINCH is robustly expressed by neurons and to a lesser degree by astrocytes in HIV infection of the CNS; whereas, in the healthy CNS, PINCH is nearly undetectable. Similarly, protein phosphatase 1α (PP1α), one of the binding partners of PINCH, is increased in the neurons of HIV encephalitis patients and co-localizes with PINCH in neurons. PINCH is a non-catalytic scaffolding protein that binds integrin-linked kinase (ILK), and PP1α and mediates Akt and GSK3β kinase activities, all of which when disrupted contribute to aberrant Tau phosphorylation. In Tat transgenic mice, increased expression levels of PINCH, PP1α and hpTau were observed. Also, in vivo manipulations of ex…
abstract: Aged HIV-positive (HIV+) individuals represent a large proportion of the HIV population as life spans are extended significantly by successful antiretroviral therapy. Increased age with HIV infection brings a unique set of central nervous system (CNS) complications including more rapid onset and progression of age-related diseases, loss of protein quality control and accumulation of aberrant proteins, such as hyperphosphorylated Tau (hpTau). In this context, we have discovered a new signaling connection between age-related neurodegeneration and HIV involving the PINCH protein. Particularly interesting new cysteine histidine-rich protein (PINCH), an adaptor protein in neuronal cells is involved in cytoskeletal organization, cell migration and cell survival. While some of the pathophysiological aspects of the PINCH-signaling cascade in tauopathy are largely conserved among neurodegenerative diseases such as Alzheimer’s disease, HIV and others, the presence of the HIV protein Tat impacts specific key points in the PINCH pathway that exacerbate CNS cell dysfunction. In virus-infected cells, Tat regulates viral replication. Even though neurons are not permissive to viral infection, the Tat protein can enter all cell types. Our studies show that Tat interferes with key PINCH signaling partners in neurons. PINCH is robustly expressed by neurons and to a lesser degree by astrocytes in HIV infection of the CNS; whereas, in the healthy CNS, PINCH is nearly undetectable. Similarly, protein phosphatase 1α (PP1α), one of the binding partners of PINCH, is increased in the neurons of HIV encephalitis patients and co-localizes with PINCH in neurons. PINCH is a non-catalytic scaffolding protein that binds integrin-linked kinase (ILK), and PP1α and mediates Akt and GSK3β kinase activities, all of which when disrupted contribute to aberrant Tau phosphorylation. In Tat transgenic mice, increased expression levels of PINCH, PP1α and hpTau were observed. Also, in vivo manipulations of ex…
author: Adiga, Radhika K.
language: eng
keywords: Neurosciences, CNS HIV, Pinch, Tau
license: http://rightsstatements.org/vocab/InC/1.0/
date published: 2015
date modified: 2026-07-27T21:20:15Z
provider: Temple University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Temple University. Libraries

PropertyValue
property ID: Handle
value: http://hdl.handle.net/20.500.12613/2528