Current Topics in Medicinal Chemistry - Volume 20, Issue 13, 2020

The fast-growing outbreak of the 2019 novel coronavirus (2019-nCoV), which originated from Wuhan locating in central China at the end of 2019, spread to multiple cities in merely a month. Although the mortality of this disease was lower than that of SARS, the incredible contagiousness was much higher than SRAS-CoV. Because of the tremendous clout of 2019-nCoV, it is essential to hold more details about it and monitor its future evolution. This mini review consequently summarizes the key elements of epidemiology features, providing updated relevant findings and novel insights related to 2019-nCoV.

Background: The central nervous system (CNS) known to regulate the physiological conditions of human body, also itself gets dynamically regulated by both the physiological as well as pathological conditions of the body. These conditions get changed quite often, and often involve changes introduced into the gut microbiota which, as studies are revealing, directly modulate the CNS via a crosstalk. This cross-talk between the gut microbiota and CNS, i.e., the gut-brain axis (GBA), plays a major role in the pathogenesis of many neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington’s disease (HD). Objective: We aim to discuss how gut microbiota, through GBA, regulate neurodegenerative disorders such as PD, AD, ALS, MS and HD. Methods: In this review, we have discussed the present understanding of the role played by the gut microbiota in neurodegenerative disorders and emphasized the probable therapeutic approaches being explored to treat them. Results: In the first part, we introduce the GBA and its relevance, followed by the changes occurring in the GBA during neurodegenerative disorders and then further discuss its role in the pathogenesis of these diseases. Finally, we discuss its applications in possible therapeutics of these diseases and the current research improvements being made to better investigate this interaction. Conclusion: We concluded that alterations in the intestinal microbiota modulate various activities that could potentially lead to CNS disorders through interactions via the GBA.

Background: The occurrence of secondary neurodegeneration has exclusively been observed after the first incidence of stroke. In humans and rodents, post-stroke secondary neurodegeneration (SND) is an inevitable event that can lead to progressive neuronal loss at a region distant to initial infarct. SND can lead to cognitive and motor function impairment, finally causing dementia. The exact pathophysiology of the event is yet to be explored. It is seen that the thalami, in particular, are susceptible to cause SND. The reason behind this is because the thalamus functioning as the relay center and is positioned as an interlocked structure with direct synaptic signaling connection with the cortex. As SND proceeds, accumulation of misfolded proteins and microglial activation are seen in the thalamus. This leads to increased neuronal loss and worsening of functional and cognitive impairment. Objective: There is a necessity of specific interventions to prevent post-stroke SND, which are not properly investigated to date owing to sparsely reproducible pre-clinical and clinical data. The basis of this review is to investigate about post-stroke SND and its updated treatment approaches carefully. Methods: Our article presents a detailed survey of advances in studies on stroke-induced secondary neurodegeneration (SND) and its treatment. Results: This article aims to put forward the pathophysiology of SND. We have also tabulated the latest treatment approaches along with different neuroimaging systems that will be helpful for future reference to explore. Conclusion: In this article, we have reviewed the available reports on SND pathophysiology, detection techniques, and possible treatment modalities that have not been attempted to date.

Background: Flavonoids, a group of natural dietary polyphenols, are known for their beneficial effects on human health. By virtue of their various pharmacological effects, like anti-oxidative, antiinflammatory, anti-carcinogenic and neuroprotective effects, flavonoids have now become an important component of herbal supplements, pharmaceuticals, medicinals and cosmetics. There has been enormous literature supporting neuroprotective effect of flavonoids. Recently their efficacy in various neurodegenerative diseases, like Alzheimer’s disease and Parkinson diseases, has received particular attention. Objective: The mechanism of flavanoids neuroprotection might include antioxidant, antiapoptotic, antineuroinflammatory and modulation of various cellular and intracellular targets. In in-vivo systems, before reaching to brain, they have to cross barriers like extensive first pass metabolism, intestinal barrier and ultimately blood brain barrier. Different flavonoids have varied pharmacokinetic characteristics, which affect their pharmacodynamic profile. Therefore, brain accessibility of flavonoids is still debatable. Methods: This review emphasized on current trends of research and development on flavonoids, especially in neurodegenerative diseases, possible challenges and strategies to encounter using novel drug delivery system. Results: Various flavonoids have elicited their therapeutic potential against neurodegenerative diseases, however by using nanotechnology and novel drug delivery systems, the bioavailability of favonoids could be enhanced. Conclusion: This study bridges a significant opinion on medicinal chemistry, ethanopharmacology and new drug delivery research regarding use of flavonoids in management of neurodegeneration.

Background: Alzheimer’s disease (AD) is one of the neurodegenerative diseases and has been hypothesized to be a protein misfolding disease. In the generation of AD, β-secretase, γ-secretase, and tau protein play an important role. A literature search reflects ever increasing interest in the design and development of anti-AD drugs targeting β-secretase, γ-secretase, and tau protein. Objective: The objective is to explore the structural aspects and role of β-secretase, γ-secretase, and tau protein in AD and the efforts made to exploit them for the design of effective anti-AD drugs. Methods: The manuscript covers the recent studies on design and development of anti-AD drugs exploiting amyloid and cholinergic hypotheses. Results: Based on amyloid and cholinergic hypotheses, effective anti-AD drugs have been searched out in which non-peptidic BACE1 inhibitors have been most prominent. Conclusion: Further exploitation of the structural aspects and the inhibition mechanism for β-secretase, γ-secretase, and tau protein and the use of cholinergic hypothesis may lead still more potent anti-AD drugs.

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.