Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Martín-Maestro, Patriciaa; b; 1 | Gargini, Ricardoa; c | García, Esthera | Simón, Dianad | Avila, Jesúsa; b; * | García-Escudero, Vegaa; b; 2; *
Affiliations: [a] Centro de Biología Molecular “Severo Ochoa” (UAM-CSIC), Cantoblanco, Madrid, Spain | [b] Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain | [c] Neuro-oncology Unit, Instituto de Salud Carlos III-UFIEC, Majadahonda, Madrid, Spain | [d] Facultad de Ciencias Experimentales, Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain
Correspondence: [*] Correspondence to: Jesús Avila and Vega García-Escudero, Centro de Biología, Molecular Severo Ochoa, Nicolás Cabrera, 1, Cantoblanco, 28049 Madrid, Spain. Tel.: +34 91 196 4564/4592; Fax: +34 91196 4420; E-mails: [email protected]; [email protected].
Note: [1] Present address: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Note: [2] Present address: Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, UAM, Madrid, Spain.
Abstract: Mitochondrial alterations and oxidative stress are common features of Alzheimer’s disease brain and peripheral tissues. Moreover, mitochondrial recycling process by autophagy has been found altered in the sporadic form of the disease. However, the contribution of the main proteins involved in this pathology such as amyloid-β protein precursor (AβPP) and tau needs to be achieved. With this aim, human unmodified fibroblasts were transduced with lentivectors encoding APP and Tau and treated with CCCP to study the mitophagy process. Both AβPP and tau separately increased autophagy flux mainly by improving degradation phase. However, in the specific case of mitophagy, labeling of mitochondria by PINK1 and PARK2 to be degraded by autophagy seemed reduced, which correlates with the long-term accumulation of mitochondria. Nevertheless, the combination of tau and AβPP was necessary to cause a mitophagy functional impairment reflected in the accumulation of depolarized mitochondria labeled by PINK1. The overexpression of Tau and APP recapitulates the mitophagy failure previously found in sporadic Alzheimer’s disease.
Keywords: Alzheimer’s disease, amyloid-β protein precursor, mitochondria, mitophagy, tau
DOI: 10.3233/JAD-190086
Journal: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 525-540, 2019
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
[email protected]
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office [email protected]
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
[email protected]
For editorial issues, like the status of your submitted paper or proposals, write to [email protected]
如果您在出版方面需要帮助或有任何建, 件至: [email protected]