Novel expression of PINCH in the central nervous system and its potential as a biomarker for human immunodeficiency virus-associated neurodegeneration.
Particularly interesting cysteine histidine-rich (PINCH) protein functions as a shuttling protein in Schwann cells after peripheral nerve damage, during repair and remodeling, and in maintaining neuronal polarity. However, the presence of PINCH in the human CNS during disease has not been addressed. Because HIV-associated damage to cells of the CNS involves dysregulation of neuronal signaling and white matter damage, we hypothesized that PINCH may play a role in neuropathological processes during the course of HIV infection. To determine the expression of PINCH in the CNS, brain, and cerebrospinal fluid (CSF) obtained at autopsy from HIV patients with no CNS alterations, HIV encephalitic (HIVE) patients, and HIV-negative individuals with no CNS alterations were examined for PINCH immunoreactivity. Our results show that PINCH is expressed robustly in the brains and CSF of HIV patients, but is nearly undetectable in HIV-negative individuals. However, HIVE patients' CSF contained significantly less PINCH than HIV patients with no CNS alterations. PINCH immunolabeling was significantly more intense in the white matter than in the grey matter and was associated exclusively with neuronal cell bodies or processes, or with the extracellular matrix. Given the recently discovered importance of PINCH in maintaining neuronal fitness, our observations that PINCH is robustly expressed in the CNS of HIV patients suggests an important role for PINCH in HIV-associated neurodegenerative processes. Understanding mechanisms by which PINCH functions during HIV-associated CNS alterations will provide new insight into potential treatments to limit neurological alterations in HIV.
Rearden
Ann
A
Department of Pathology, University of California San Diego, La Jolla, California, USA.
Hurford
Rosemary
R
Luu
Nhan
N
Kieu
Emily
E
Sandoval
Melissa
M
Perez-Liz
Georgina
G
Del Valle
Luis
L
Powell
Henry
H
Langford
T Dianne
TD
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D005455:Fluorescent Antibody Technique; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C088088:LIMS1 protein, human; D008565:Membrane Proteins