Inhibition of HDAC6 activity protects dopaminergic neurons from alpha-synuclein toxicity

• Verfasst von: Francelle, Laetitia [VerfasserIn]
• Verfasst von: Outeiro, Tiago F. [VerfasserIn]
• Verfasst von: Rappold, Gudrun [VerfasserIn]
• Titel: Inhibition of HDAC6 activity protects dopaminergic neurons from alpha-synuclein toxicity
• Verf.angabe: Laetitia Francelle, Tiago F. Outeiro & Gudrun A. Rappold
• E-Jahr: 2020
• Jahr: 8 April 2020
• Umfang: 14 S.
• Fussnoten: Gesehen am 23.09.2020
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2020
• Band/Heft Quelle: 10(2020) Artikel-Nummer 6064, 14 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-020-62678-5
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1733602402

Abstract

The neuropathological hallmarks of Parkinson’s disease include preferential vulnerability of dopaminergic neurons of the substantia nigra pars compacta, and accumulation of intraneuronal protein inclusions known as Lewy bodies. These inclusions contain, among other proteins, aggregated alpha-synuclein and histone deacetylase 6 (HDAC6). In our study we found that selective inhibition of HDAC6 activity by Tubastatin A has protective effects in a rat model of Parkinson’s disease. We provide evidence that this protection may be due to the activation of chaperone-mediated autophagy through the up-regulation of key members of this pathway. Moreover, Tubastatin A significantly inhibited the expression of a toxic form of alpha-synuclein that is phosphorylated at serine position 129. Tubastatin A treatment also permitted to partially modulate neuroinflammation. Taken together, our study highlights the neuroprotective effects of Tubastatin A in a rat model of Parkinson’s disease and provides mechanistic insight in Tubastatin A-mediated protection against alpha-synuclein toxicity and substantia nigra degeneration. These findings are of potential therapeutic value in Parkinson’s disease and other synucleinopathies.