Cellular senescence and Alzheimer disease: the egg and the chicken scenario
Saez-Atienzar S, Masliah E. Cellular senescence and Alzheimer disease: the egg and the chicken scenario. Nat Rev Neurosci. 2020 Aug;21(8):433-444. doi: 10.1038/s41583-020-0325-z. Epub 2020 Jun 29. Erratum in: Nat Rev Neurosci. 2020 Oct;21(10):587. PMID: 32601397.
It is hard to know whether the accumulation of senescent cells is the cause or result of AD-related disease.
- p53: controls the activation of pro-apoptotic regulators in response to cell damage
- p21: induce senescence to control milder damage p26: marks a further senescent
- stage; inhibits CDK4 and CDK6 leading to long-lasting arrest of the cell cycle
Senescence is helpful when there is an acute insult, but when the problem is chronic, it can be cytotoxic.
If senescent cells are not cleared, they enter a stage called late senescene which that is associated with neurodegeneration. Senescent cells can spread senescent signals to their neighbours and induce senescence - bystander effect. This could account for how post-mitotic cells enter senescence.
Are any known or yettobe discovered genetic risk loci associated with AD involved in the senescence pathway?