Astrocytic centrin-2 expression in entorhinal cortex correlates with Alzheimer's disease severity.

Autor: Degl'Innocenti E; Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy.; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Poloni TE; Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, Italy., Medici V; Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, Italy., Olimpico F; Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy., Finamore F; Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy., Profka X; Department of Neurology and Neuropathology, Golgi-Cenci Foundation & ASP Golgi-Redaelli, Abbiategrasso, Italy., Bascarane K; Laboratoire des Maladies Neurodégénératives, Université Paris-Saclay, CEA, CNRS, MIRCen, Fontenay-aux-Roses, France., Morrone C; Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy., Pastore A; Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy.; Laboratorio NEST, Scuola Normale Superiore, Pisa, Italy., Escartin C; Laboratoire des Maladies Neurodégénératives, Université Paris-Saclay, CEA, CNRS, MIRCen, Fontenay-aux-Roses, France., McDonnell LA; Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy., Dell'Anno MT; Fondazione Pisana per la Scienza ONLUS, San Giuliano Terme, Italy.
Jazyk: angličtina
Zdroj: Glia [Glia] 2024 Dec; Vol. 72 (12), pp. 2158-2177. Date of Electronic Publication: 2024 Aug 15.
DOI: 10.1002/glia.24603
Abstrakt: Astrogliosis is a condition shared by acute and chronic neurological diseases and includes morphological, proteomic, and functional rearrangements of astroglia. In Alzheimer's disease (AD), reactive astrocytes frame amyloid deposits and exhibit structural changes associated with the overexpression of specific proteins, mostly belonging to intermediate filaments. At a functional level, amyloid beta triggers dysfunctional calcium signaling in astrocytes, which contributes to the maintenance of chronic neuroinflammation. Therefore, the identification of intracellular players that participate in astrocyte calcium signaling can help unveil the mechanisms underlying astrocyte reactivity and loss of function in AD. We have recently identified the calcium-binding protein centrin-2 (CETN2) as a novel astrocyte marker in the human brain and, in order to determine whether astrocytic CETN2 expression and distribution could be affected by neurodegenerative conditions, we examined its pattern in control and sporadic AD patients. By immunoblot, immunohistochemistry, and targeted-mass spectrometry, we report a positive correlation between entorhinal CETN2 immunoreactivity and neurocognitive impairment, along with the abundance of amyloid depositions and neurofibrillary tangles, thus highlighting a linear relationship between CETN2 expression and AD progression. CETN2-positive astrocytes were dispersed in the entorhinal cortex with a clustered pattern and colocalized with reactive glia markers STAT3, NFATc3, and YKL-40, indicating a human-specific role in AD-induced astrogliosis. Collectively, our data provide the first evidence that CETN2 is part of the astrocytic calcium toolkit undergoing rearrangements in AD and adds CETN2 to the list of proteins that could play a role in disease evolution.
(© 2024 The Author(s). GLIA published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: