Impaired capacity to restore proteostasis in the aged brain after ischemia: Implications for translational brain ischemia research.

07:00 EST 29th December 2018 | BioPortfolio

Summary of "Impaired capacity to restore proteostasis in the aged brain after ischemia: Implications for translational brain ischemia research."

Brain ischemia induced by cardiac arrest or ischemic stroke is a severe form of metabolic stress that substantially disrupts cellular homeostasis, especially protein homeostasis (proteostasis). As proteostasis is fundamental for cellular and organismal health, cells have developed a complex network to restore proteostasis impaired by stress. Many components of this network - including ubiquitination, small ubiquitin-like modifier (SUMO) conjugation, autophagy, and the unfolded protein response (UPR) - are activated in the post-ischemic brain, and play a crucial role in cell survival and recovery of neurologic function. Importantly, recent studies have shown that ischemia-induced activation of these proteostasis-related pathways in the aged brain is impaired, indicating an aging-related decline in the self-healing capacity of the brain. This impaired capacity is a significant factor for consideration in the field of brain ischemia because the vast majority of cardiac arrest and stroke patients are elderly. In this review, we focus on the effects of aging on these critical proteostasis-related pathways in the brain, and discuss their implications in translational brain ischemia research.


Journal Details

This article was published in the following journal.

Name: Neurochemistry international
ISSN: 1872-9754


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Medical and Biotech [MESH] Definitions

A disorder characterized by a reduction of oxygen in the blood combined with reduced blood flow (ISCHEMIA) to the brain from a localized obstruction of a cerebral artery or from systemic hypoperfusion. Prolonged hypoxia-ischemia is associated with ISCHEMIC ATTACK, TRANSIENT; BRAIN INFARCTION; BRAIN EDEMA; COMA; and other conditions.

A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES; or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.

Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.

Constriction of arteries in the SKULL due to sudden, sharp, and often persistent smooth muscle contraction in blood vessels. Intracranial vasospasm results in reduced vessel lumen caliber, restricted blood flow to the brain, and BRAIN ISCHEMIA that may lead to hypoxic-ischemic brain injury (HYPOXIA-ISCHEMIA, BRAIN).

Brain dysfunction or damage resulting from sustained MALIGNANT HYPERTENSION. When BLOOD PRESSURE exceeds the limits of cerebral autoregulation, cerebral blood flow is impaired (BRAIN ISCHEMIA). Clinical manifestations include HEADACHE; NAUSEA; VOMITING; SEIZURES; altered mental status (in some cases progressing to COMA); PAPILLEDEMA; and RETINAL HEMORRHAGE.

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