Title:Peripheral Mononuclear Cell Rejuvenation for Senescence Surveillance in Alzheimer Disease
Volume: 19
Issue: 9
Author(s): Marco Malavolta, Andrea Basso, Francesco Piacenza, Laura Costarelli, Robertina Giacconi and Eugenio Mocchegiani
Affiliation:
Keywords:
Cell senescence, Alzheimer, peripheral mononuclear phagocytes, microglia, rejuvenation, astrocytes, sporadic AD, neurodegeneration, CNS, innate immunity
Abstract: Recent observations have pointed out that microglia, astrocytes and cerebrovascular endothelial cells senescence might contribute
to the onset or progression of sporadic AD. The accumulation of senescent dysfunctional microglia or senescence related changes
of other cells within CNS could be causally implicated in AD and age-related dysfunction and their efficient removal could represent a
pivotal mechanism to prevent or delay neurodegeneration. The question how senescent cells are cleared from CNS has been poorly investigated,
even though it is reasonable to believe that resident microglia is involved in this task. However, accumulating evidence now support
the idea that assistance by peripheral mononuclear phagocytes (MP) in AD could be essential to control local brain inflammation and
remove Abeta depots. Based on the current knowledge it is reasonable to hypothesize that senescence surveillance might be among the
tasks that blood derived MP are called to envelop in the CNS during particular conditions, especially in the case senescent microglia is
not able to achieve this task properly. However, age-related dysfunctions of these players of innate immunity could lead to depict a series
of events that synergically with microglia and other CNS cells senescence could lead to a rapid progression of the disease. Hence, the design
of intervention aimed at targeting accumulating senescent cells by rejuvenation of peripheral MP function seems an attractive tool
that perhaps would also help to clarify the processes involved in senescence surveillance in normal and AD brain.
