Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.

Nanocarrier mediated drug delivery as an impeccable therapeutic approach against Alzheimer's disease.

For the past several years, dementia, is one of the predominantly observed groups of symptoms in a geriatric population. Alzheimer's disease (AD) is a progressive memory related neurodegenerative disease, for which the current Food and drug administration approved therapeutics are only meant for a symptomatic management rather than targeting the root cause of AD. These therapeutics belong to two classes, Acetylcholine Esterase inhibitors and N-methyl D-aspartate antagonist. Furthermore, to facilitate neuroprotective action in AD, the drugs are majorly expected to reach the specific target area in the brain for the desired efficacy. Thus, there is a huge requirement for drug discovery and development for facilitating the entry of drugs more in brain to exert a specific action. The very first line of defense and the major limitation for the entry of drugs into the brain is the Blood Brain Barrier, followed by Blood-Cerebrospinal Fluid Barrier. More than a barrier, these mainly act as selectively permeable membranes, which allows entry of specific molecules into the brain. Furthermore, specific enzymes result in the degradation of xenobiotics. All these mechanisms pose as hurdles in the way of effective drug delivery in the brain. Thus, novel techniques need to be harbored for the facilitation of the delivery of such drugs into the brain. Nanocarriers are advantageous for facilitating the specific targeted drug treatment in AD. As nanomedicines are one of the novels and most useful approaches for AD, thus the present review mainly focuses on understanding the advanced use of nanocarriers for targeted drug delivery in the management of AD.

Epigenetics in Neurodegenerative Diseases: The Role of Histone Deacetylases.

BACKGROUND & OBJECTIVE: Imbalance in histone acetylation levels and consequently the dysfunction in transcription are associated with a wide variety of neurodegenerative diseases. Histone proteins acetylation and deacetylation is carried out by two opposite acting enzymes, histone acetyltransferases and histone deacetylases (HDACs), respectively. In-vitro and in-vivo animal models of neurodegenerative diseases and post mortem brains of patients have been reported overexpressed level of HDACs. In recent past numerous studies have indicated that HDAC inhibitors (HDACIs) might be a promising class of therapeutic agents for treating these devastating diseases. HDACs being a part of repressive complexes, the outcome of their inhibition has been attributed to enhanced gene expression due to heightened histone acetylation. Beneficial effects of HDACIs has been explored both in preclinical and clinical studies of these diseases. Thus, their screening as future therapeutics for neurodegenerative diseases has been widely explored. CONCLUSION: In this review, we focus on the putative role of HDACs in neurodegeneration and further discuss their potential as a new therapeutic avenue for treating neurodegenerative diseases.