Changes in PINCH levels in the CSF of HIV+ individuals correlate with hpTau and CD4 count

Adiga, Radhika; Ozdemir, Ahmet Yunus; Carides, Alexandra D.; Wasilewski, M; Yen, William; Chitturi, Pallavi; Ellis, Ronald J.; Langford, Dianne

doi:10.1007/s13365-014-0252-8

Cited by 5 publications

(6 citation statements)

References 36 publications

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“…Further studies revealed that PINCH and hpTau bind one another, and that this interaction may be important for the regulation of hpTau’s interaction with heat shock machinery [40]. In other studies, changes in the levels of PINCH and hpTau in CSF of HIV patients were shown to correlate directly with one another [1]. Taken together, results from this study and others support an important role for PINCH in tau phosphorylation.…”

Section: Discussionsupporting

confidence: 70%

“…Recently identified as a binding partner of hpTau, the PINCH protein [1,27,40,44] is involved in protein recruitment, protein complex assembly and shuttling throughout the cell (for review, see [29]). During brain development, PINCH is expressed at high levels and functions in cytoskeletal organization and communication between the cell and the extracellular matrix [32,33].…”

Section: Discussionmentioning

confidence: 99%

“…In fact, recent studies show that PINCH interacts with hpTau and may influence its clearance via interactions with the heat shock machinery [40]. Recent studies in HIV show that changes in CSF levels of hpTau are mirrored by changes in PINCH [1].…”

Section: Introductionmentioning

confidence: 99%

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Dysregulation of PINCH signaling in mesial temporal epilepsy

Liu

Russin

Heck

et al. 2017

Journal of Clinical Neuroscience

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Mounting evidence suggests that inflammation is important in epileptogenesis. Particularly Interesting New Cysteine Histidine-rich (PINCH) protein is a highly conserved, LIM-domain protein known to interact with hyperphosphorylated Tau. We assessed PINCH expression in resected epileptogenic human hippocampi and further explored the relationships among PINCH, hpTau and associated kinases. Resected hippocampal tissue from 7 patients with mesial temporal lobe epilepsy (MTLE) was assessed by Western analyses to measure levels of PINCH and hyperphosphorylated Tau, as well as changes in phosphorylation levels of associated kinases AKT and GSK3β in comparison to normal control tissue. Immunolabeling was also conducted to evaluate PINCH and hpTau patterns of expression, co-localization and cell-type specific expression. Hippocampal PINCH was increased by 2.6 fold in the epilepsy cases over controls and hpTau was increased 10 fold over control. Decreased phospho-AKT and phospho-GSK3β in epilepsy tissue suggested involvement of this pathway in MTLE. PINCH and hpTau co-localized in some neurons in MTLE tissue. While PINCH was expressed by both neurons and astrocytes in MTLE tissue, hpTau was extracellular or associated with neurons. PINCH was absent from the serum of control subjects but readily detectable from the serum of patients with chronic epilepsy. Our study describes the expression of PINCH and points to AKT/GSK3β signaling dysregulation as a possible pathway in hpTau formation in MTLE. In view of the interactions between hpTau and PINCH, understanding the role of PINCH in MTLE may provide increased understanding of mechanisms leading to inflammation and MTLE epileptogenesis and a potential biomarker for drug-resistant epilepsy.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

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Dysregulation of PINCH signaling in mesial temporal epilepsy

Liu

Russin

Heck

et al. 2017

Journal of Clinical Neuroscience

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“…These surrogate markers are believed to reflect the amount of abnormal Tau present in the brain and CSF. In particular, the LIM-domain only protein PINCH has gained some recent attention (Adiga et al, 2014; Ozdemir et al, 2013), but it remains to be seen if this protein truly correlates with the levels of abnormal Tau in the brain and CSF, and/or if it can be used to predict cumulative damage after repetitive TBI.…”

Section: Perspectives Future Directions and Conclusionmentioning

confidence: 99%

Blood biomarkers for brain injury: What are we measuring?

Kawata

Liu

Merkel

et al. 2016

Neuroscience & Biobehavioral Reviews

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187

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Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury.

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“…53 Unexpectedly, the amount of PINCH in CSF did not display a positive correlation with the CSF virus burden, but was related to the immune responses in patients. 54 Further studies are required to reveal the exact role and significance of PINCH in central nervous system diseases induced by HIV infection.…”

Section: Pinch and Binding Partnersmentioning

confidence: 99%

Signaling via PINCH: Functions, binding partners and implications in human diseases

Cao

Xiao

2016

Gene

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Particularly interesting new cysteine-histidine-rich protein (PINCH) is a LIM-domain-only adaptor that plays important roles in cytoskeletal organization and extracellular matrix adhesion, migration, proliferation and survival. Mammalian cells have two functional PINCH proteins, PINCH1 and PINCH2. PINCH not only binds to Nck2 and engages in the signaling of growth factor receptors, but also forms a ternary complex with ILK and parvin (IPP complex). Normally, the IPP complex locates to focal adhesions participating in the signaling of integrins and mediating the interaction of cytoskeleton and extracellular matrix (ECM). Accumulative evidence indicates that abnormalities in PINCH signaling are involved in the pathogenesis of important diseases, such as cancers, renal diseases, cardiomyopathy, and HIV. Therefore, clarifying the functions of PINCH and its interactions with key factors is important for better understanding of signaling events both in health and disease.

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Changes in PINCH levels in the CSF of HIV+ individuals correlate with hpTau and CD4 count

Cited by 5 publications

References 36 publications

Dysregulation of PINCH signaling in mesial temporal epilepsy

Dysregulation of PINCH signaling in mesial temporal epilepsy

Blood biomarkers for brain injury: What are we measuring?

Signaling via PINCH: Functions, binding partners and implications in human diseases

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