4.2 Article

Calcium Signalling Toolkits in Astrocytes and Spatio-Temporal Progression of Alzheimer's Disease

Journal

CURRENT ALZHEIMER RESEARCH
Volume 13, Issue 4, Pages 359-369

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567205013666151116130104

Keywords

Alzheimer's disease; astrocyte; astroglial atrophy; astrogliosis; calcium signaling; glutamate receptors; InsP(3) receptors; neuroglia; beta-amyloid

Funding

  1. Fondazione Cariplo [2008-2319, 2014-1094]
  2. MiUR (PRIN
  3. SynAD)
  4. Alzheimer's Research Trust (UK)
  5. European Commission
  6. IKERBASQUE
  7. Ministry of Education and Science of the Russian Federation [02.B.49.21.0003]
  8. Lobachevsky State University of Nizhny Novgorod
  9. Russian Scientific Foundation [14-15-00633]
  10. Ministry of education of Russian Federation [RFMEFI57814X0079]
  11. National Institutes of Health (The Eunice Kennedy Shriver National Institute of Child Health and Human Development award) [HD078678]
  12. Slovenian Research Agency (ARRS) [P3 310, J3 4051, J3 3632, J36790, J3 4146]
  13. EduGlia ITN EU grant
  14. CAPES
  15. EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R21HD078678] Funding Source: NIH RePORTER

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Pathological remodelling of astroglia represents an important component of the pathogenesis of Alzheimer's disease (AD). In AD astrocytes undergo both atrophy and reactivity; which may be specific for different stages of the disease evolution. Astroglial reactivity represents the generic defensive mechanism, and inhibition of astrogliotic response exacerbates b-amyloid pathology associated with AD. In animal models of AD astroglial reactivity is different in different brain regions, and the deficits of reactive response observed in entorhinal and prefrontal cortices may be linked to their vulnerability to AD progression. Reactive astrogliosis is linked to astroglial Ca2+ signalling, this latter being widely regarded as a mechanism of astroglial excitability. The AD pathology evolving in animal models as well as acute or chronic exposure to beta-amyloid induce pathological remodelling of Ca2+ signalling toolkit in astrocytes. This remodelling modifies astroglial Ca2+ signalling and may be linked to cellular mechanisms of AD pathogenesis.

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