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2019 | 79 | Suppl.1 |
Tytuł artykułu

Mitochondrial integrity and function in model systems of CNS diseases

Autorzy
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
Mitochondria are key regulators of energy metabolism, redox balance, calcium homeostasis, and programmed cell death. In the past, we characterized mitochondria acting as targets of both caspase-dependent and caspase- independent death signalling triggered by increased oxidative stress and as executioners of programmed death signalling in neurons. For example, we identified mitochondrial damage in caspase‑independent neuronal death after cerebral ischemia in vivo, and in oxidative cell death, i.e., ferroptosis in vitro. Protective intervention against oxidative damage further confirmed the conclusion that mitochondria represent the “point of no return” in caspase‑independent paradigms of programmed cell death. Further, we found more recently that mitochondri al-targeted alpha-synuclein caused severe mitochondrial toxicity and caspase-dependent cell death in human dopaminergic neurons, a model system relevant to Parkinson’s disease. In different model systems of neuronal death, neuroprotective interference with mitochondrial pathways of programmed cell death was frequently attributed to metabolic switches, i.e., reduced mitochondrial respiration and increased glycolytic activity. Accordingly, targeting metabolic switches may serve as a general strategy for mitochondrial protection and, thereby, neuroprotection, but may also affect mechanisms of neuroinflammation involving activation of microglia. The understanding of the underlying mechanism of such metabolic protection may reveal novel therapeutic targets in neural diseases featuring mitochondrial impairments and neuroinflammation.
Wydawca
-
Rocznik
Tom
79
Numer
Opis fizyczny
p.XXIV
Twórcy
autor
  • Institute of Pharmacology and Clinical Pharmacy, University of Marburg, Marburg, Germany
  • Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-00d92a3a-79ad-4262-9266-916024be6bbc
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