Astrocytic pathological calcium homeostasis and impaired vesicle trafficking in neurodegeneration
Vardjan, Nina (Author), Verkhratsky, Alexei (Author), Zorec, Robert (Author)

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Although the central nervous system (CNS) consists of highly heterogeneous populations of neurones and glial cells, clustered into diverse anatomical regions with specific functions, there are some conditions, including alertness, awareness and attention that require simultaneous, coordinated and spatially homogeneous activity within a large area of the brain. During such events, the brain, representing only about two percent of body mass, but consuming one fifth of body glucose at rest, needs additional energy to be produced. How simultaneous energy procurement in a relatively extended area of the brain takes place is poorly understood. This mechanism is likely to be impaired in neurodegeneration, for example in Alzheimer’s disease, the hallmark of which is brain hypometabolism. Astrocytes, the main neural cell type producing and storing glycogen, a form of energy in the brain, also hold the key to metabolic and homeostatic support in the central nervous system and are impaired in neurodegeneration, contributing to the slow decline of excitation-energy coupling in the brain. Many mechanisms are affected, including cell-to-cell signalling. An important question is how changes in cellular signalling, a process taking place in a rather short time domain, contribute to the neurodegeneration that develops over decades. In this review we focus initially on the slow dynamics of Alzheimer’s disease, and on the activity of locus coeruleus, a brainstem nucleus involved in arousal. Subsequently, we overview much faster processes of vesicle traffic and cytosolic calcium dynamics, both of which shape the signalling landscape of astrocyte-neurone communication in health and neurodegeneration.

Keywords:Alzheimer's disease, Parkinson's disease, neurodegeneration, astrocyte, glia, vesicle traffic, calcium homeostasis, cAMP, neurodegeneration, locus coeruleus, noradrenaline, excitation-energy coupling
Work type:Article (dk_c)
Tipology:1.02 - Review Article
Organization:MF - Faculty of Medicine
Number of pages:19 str.
Numbering:Vol. 18, iss. 2, art. 358
ISSN on article:1422-0067
DOI:10.3390/ijms18020358 This link opens in a new window
COBISS.SI-ID:33094617 This link opens in a new window
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Record is a part of a journal

Title:International journal of molecular sciences
Shortened title:Int. j. mol. sci.
COBISS.SI-ID:2779162 This link opens in a new window

Document is financed by a project

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:P3-0310
Name:Celična fiziologija

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J3-3632
Name:Molekularne lastnosti fuzijske pore

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J3-4051
Name:Vloga monomernih GTPaz pri uravnavanju mobilnosti endosomov/lizosomov v astrocitih

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J3-4146
Name:Mobilnost sekrecijskih mešičkov in homeostaza kalcija v astrocitih

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J3-6790
Name:Dinamične meritve metabolitov in sekundarnih prenašalcev v posameznem astrocitu v celični kulturi

Funder:ARRS - Agencija za raziskovalno dejavnost Republike Slovenije (ARRS)
Project no.:J3-7605
Name:Nanofiziologija eksocitoze v zdravih in bolezenskih razmerah

Funder:Drugi - Drug financer ali več financerjev
Funding Programme:COST
Project no.:CM1207


License:CC BY 4.0, Creative Commons Attribution 4.0 International
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:08.02.2017

Secondary language

Keywords:Alzheimerjeva bolezen, Parkinsonova bolezen, nevrodegeneracija

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