No abstract

The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

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The worldwide prevalence of movement disorders is increasing day by day. Parkinson's disease (PD) is the most common movement disorder. In general, the clinical manifestations of PD result from dysfunction of the basal ganglia. Although the exact underlying mechanisms leading to neural cell death in this disease remains unknown, the genetic causes are often established. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the neurological disease conditions. The acetylation and deacetylation of histone proteins are carried out by opposing actions of histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. In the recent past, studies with HDAC inhibitors result in beneficial effects in both in vivo and in vitro models of PD. Various clinical trials have also been initiated to investigate the possible therapeutic potential of HDAC inhibitors in patients suffering from PD. The possible mechanisms assigned for these neuroprotective actions of HDAC inhibitors involve transcriptional activation of neuronal survival genes and maintenance of histone acetylation homeostasis, both of which have been shown to be dysregulated in PD. In this review, the authors have discussed the putative role of HDAC inhibitors in PD and associated abnormalities and suggest new directions for future research in PD.

Metabolic syndrome is increasingly recognized for its effects on cognitive health. Recent studies have highlighted the role of histone deacetylases (HDACs) in metabolic syndrome and cognitive functions. The present study was designed to investigate the possible therapeutic role of a HDAC inhibitor, trichostatin A (TSA), in cognitive impairment associated with metabolic syndrome. To ascertain the mechanisms involved, we fed mice with high-fat diet (HFD) for 4 weeks and examined changes in behavioral and biochemical/oxidative stress markers. Mice subjected to HFD exhibited characteristic features of metabolic disorder, viz., hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and lower high-density lipoprotein (HDL) cholesterol levels. Moreover, these mice showed severe deficits in learning and memory as assessed by the Morris water maze and passive avoidance tasks along with elevated oxidative stress and inflammatory markers in brain homogenates. The observed changes occurred concurrently with reduced brain-derived neurotrophic factor (BDNF). In contrast, the mice treated with the HDAC inhibitor, TSA (0.5 and 1 mg/kg, i.p.), showed a significant and dose-dependent reduction in serum glucose, triglycerides, and total cholesterol along with improvement in HDL-cholesterol levels and learning and memory performance. TSA treatment also results in alleviation of oxidative stress and neuroinflammatory markers. Moreover, TSA significantly augmented the BDNF levels in HFD-fed mice. Thus, based upon these observations, it may be suggested that HDAC inhibition could be a novel therapeutic strategy to combat cognitive impairment associated with metabolic syndrome.