Does autophagy worsen or improve the survival of dopaminergic neurons?

Parkinsonism & Related Disorders
Livia PasqualiFrancesco Fornai

Abstract

In eukaryotic cells intracellular components are mainly degraded by autophagy and the ubiquitin-proteasome system. Autophagy is more flexible compared with the ubiquitin-proteasome system and it is involved in the degradation of long-lived proteins and organelles, such as mitochondria, which cannot be degraded by the ubiquitin-proteasome. Although autophagy is able to compensate for ubiquitin-proteasome dysfunction, the opposite does not occur. Autophagy is frequently involved in neurodegeneration; however, there is no consensus on its role in cell survival, as it can be either neuroprotective or neurotoxic. With respect to dopaminergic neurons, there is evidence that autophagy occurs during damage to substantia nigra neurons such as in Parkinson's disease. Moreover, a variety of inherited forms of Parkinson's disease are characterized by mutated proteins that belong to the autophagy pathway. Inhibition of autophagy precipitates dopaminergic cell death, whereas autophagy activation rescues the death of nigral dopaminergic neurons induced by proteasome inhibitors. Taken together, this evidence suggests that autophagy improves the survival of dopaminergic cells.

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Citations

Oct 1, 2013·Cell Biology and Toxicology·Hui-Hsing HungChien-Yuan Pan
Aug 7, 2016·Frontiers in Neuroanatomy·Paola LenziFrancesco Fornai
Dec 29, 2017·Molecular Neurodegeneration·Zhiqiang DengZhenyu Yue
Aug 1, 2018·International Journal of Molecular Sciences·Larisa RyskalinFrancesco Fornai
May 8, 2019·International Journal of Molecular Sciences·Fiona LimanaqiFrancesco Fornai
Apr 27, 2016·Medicinal Research Reviews·Chiara VidoniCiro Isidoro
Jul 7, 2019·International Journal of Molecular Sciences·Fiona LimanaqiFrancesco Fornai
Aug 5, 2011·Prion·Gianfranco NataleFrancesco Fornai
Jun 11, 2021·Journal of Neural Transmission·Francesca BiagioniFrancesco Fornai

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