Is age a key factor contributing to the disparity between success of neuroprotective strategies in young animals and limited success in elderly stroke patients? Focus on protein homeostasis
Year: 2017
Type: article
Abstract: Neuroprotection strategies to improve stroke outcome have been successful in the laboratory but not in clinical stroke trials, and thus have come under scrutiny by the medical community. Experimental stroke investigators are therefore under increased pressure to resolve this problem. Acute ischemic stroke represents a severe form of metabolic stress that activates many pathological processes and thereby impairs cellular functions. Traditionally, neuroprotection strategies were designed to improve stroke outcome by interfering with pathological processes triggered by ischemia. However, stroke outcome is also dependent on the brain's capacity to restore cellular functions impaired by ischemia, and this capacity declines with age. It is, therefore, conceivable that this age-dependent decline in the brain's self-healing capacity contributes to the disparity between the success of neuroprotective strategies in young animals, and limited success in elderly stroke patients. Here, prosurvival pathways that restore protein homeostasis impaired by ischemic stress should be considered, because their capacity decreases with increasing age, and maintenance of proteome fidelity is pivotal for cell survival. Boosting such prosurvival pathways pharmacologically to restore protein homeostasis and, thereby, cellular functions impaired by ischemic stress is expected to counterbalance the compromised self-healing capacity of aged brains and thereby help to improve stroke outcome.
Authors: Wei Yang, Wulf Paschen
Institutions: Duke University, Duke Medical Center
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1207052624, G4045056121
OpenAlex ID: W2741518211