Compromised autophagy and mitophagy in brain ageing and Alzheimer’s diseases
Domenica Caponio,
Kateřina Veverová,
Shi-qi Zhang,
Liu Shi,
Garry Wong,
Martin Vyhnalek,
Evandro F. Fang
Affiliations
Domenica Caponio
Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway
Kateřina Veverová
Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
Shi-qi Zhang
Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway
Liu Shi
Department of Psychiatry, University of Oxford, Oxford, UK; Novo Nordisk Research Centre Oxford (NNRCO)
Garry Wong
Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau 999078, China
Martin Vyhnalek
Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic; Corresponding authors at: Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway (E.F. Fang).
Evandro F. Fang
Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway; The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway; Corresponding authors at: Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway (E.F. Fang).
Alzheimer’s disease (AD) is one of the most persistent and devastating neurodegenerative disorders of old age, and is characterized clinically by an insidious onset and a gradual, progressive deterioration of cognitive abilities, ranging from loss of memory to impairment of judgement and reasoning. Despite years of research, an effective cure is still not available. Autophagy is the cellular ‘garbage’ clearance system which plays fundamental roles in neurogenesis, neuronal development and activity, and brain health, including memory and learning. A selective sub-type of autophagy is mitophagy which recognizes and degrades damaged or superfluous mitochondria to maintain a healthy and necessary cellular mitochondrial pool. However, emerging evidence from animal models and human samples suggests an age-dependent reduction of autophagy and mitophagy, which are also compromised in AD. Upregulation of autophagy/mitophagy slows down memory loss and ameliorates clinical features in animal models of AD. In this review, we give an overview of autophagy and mitophagy and their link to the progression of AD. We also summarize approaches to upregulate autophagy/mitophagy. We hypothesize that age-dependent compromised autophagy/mitophagy is a cause of brain ageing and a risk factor for AD, while restoration of autophagy/mitophagy to more youthful levels could return the brain to health.
