Aiming for the Target: Mitochondrial Drug Delivery in Traumatic Brain Injury.

Aiming for the Target: Mitochondrial Drug Delivery in Traumatic Brain Injury. Neuropharmacology. 2018 Jul 12;: Authors: Lamade AM, Kenny EM, Anthonymuthu TS, Soysal E, Clark R, Kagan VE, Bayır H Abstract Mitochondria are a keystone of neuronal function, serving a dual role as sustainer of life and harbinger of death. While mitochondria are indispensable for energy production, a dysregulated mitochondrial network can spell doom for both neurons and the functions they provide. Traumatic brain injury (TBI) is a complex and biphasic injury, often affecting children and young adults. The primary pathological mechanism of TBI is mechanical, too rapid to be mitigated by anything but prevention. However, the secondary injury of TBI evolves over hours and days after the initial insult providing a window of opportunity for intervention. As a nexus point of both survival and death during this second phase, targeting mitochondrial pathology in TBI has long been an attractive strategy. Often these attempts are mired by efficacy-limiting unintended off-target effects. Specific delivery to and enrichment of therapeutics at their submitochondrial site of action can reduce deleterious effects and increase potency. Mitochondrial drug localization is accomplished using (1) the mitochondrial membrane potential, (2) affinity of a carrier to mitochondria-specific components (e.g. lipids), (3) piggybacking on the cells own mitochondria trafficking systems...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research