Description

Histone deacetylase 6 inhibitors (HDAC6is) have been applied to certain cancer diseases and more recently to central nervous system (CNS) disorders including Rett syndrome, Alzheimer's and Parkinson's diseases, and major depressive disorder. Brain penetrance is the major challenge for the development of HDAC6is as potential therapeutics for CNS disorders due in part to the polarity of hydroxamate ZBG. Hence, only a handful of brain-penetrant HDAC6is have been reported and a few display appropriate in vitro and in vivo activities in models of neurological diseases in last decades. Severe depressive disorder (SDD) has been characterized by abnormal brain activity and interactions across the whole-brain functional networks. Electroconvulsive therapy (ECT) has been considered as an effective and rapid treatment for SDD. However, whether ECT may enhance the dysconnectivity between brain networks to achieve antidepressant effects is still largely unknown.

Therapeutic conveyance into the brain is a cardinal requirement for treatment of diverse central nervous system (CNS) disorders and associated pathophysiology. Effectual shielding of the brain by the blood-brain barrier (BBB) sieves out major proportion of therapeutics with the exception of small lipophilic molecules. Various nano-delivery systems (NDS) provide an effective solution around this obstacle owing to their small size and targeting properties. To date, these systems have been used for several pre-clinical disease models including glioma, neurodegenerative diseases and psychotic disorders. An efficacy screen for these systems involves a test battery designed to probe into the multiple facets of therapeutic delivery. Despite their wide application in redressing various disease targets, the efficacy evaluation strategies for all can be broadly grouped into four modalities, namely: histological, bio-imaging, molecular and behavioural

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With Regards
Clara
Journal Coordinator
Journal of Annals of Behavioural Science