| Autor: |
Wang H; Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, Norway., Lautrup S; Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, Norway., Caponio D; Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, Norway., Zhang J; Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, Norway.; Xiangya School of Stomatology, Central South University, Changsha 410083, China., Fang EF; Department of Clinical Molecular Biology, Akershus University Hospital, University of Oslo, 1478 Lørenskog, Norway.; The Norwegian Centre on Healthy Ageing (NO-Age), 0010 Oslo, Norway. |
| Abstrakt: |
DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA ), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB , respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM ), and Werner syndrome (WS, with most cases caused by mutations in WRN ). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD + ), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer's disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD. |
