Neuroprotective methodologies in treatment of Multiple Sclerosis: Current status of Clinical and Pre-clinical findings

2020 ◽  
Vol 17 ◽  
Author(s):  
Tarun Kapoor ◽  
Sidharth Mehan
Keyword(s):  
Multiple Sclerosis ◽  
Brain Regions ◽  
Clinical Findings ◽  
Adenyl Cyclase ◽  
Current Status ◽  
Interferon Β ◽  
Pharmacological Interventions ◽  
Motor Neuron Disorder ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds

: Multiple sclerosis an idiopathic and autoimmune associated motor neuron disorder that attacks myelinated neurons in specific brain regions of young people, especially females; characterized by oligodendrocytes destruction causes demyelination, neuroinflammation, mitochondrial abnormalities, oxidative stress and neurotransmitter deficits associated with motor and cognitive dysfunctions, vertigo and muscle weakness. The limited intervention of pharmacologically active compounds like interferon-β, mitoxantrone, fingolimod and monoclonal antibodies used clinically are majorly associated with adverse drug reactions. Pre-clinically, gliotoxin ethidium bromide mimics the behavioral and neurochemical alterations in multiple sclerosis like experimental animals associated with the down regulation of adenyl cyclase/cAMP/CREB further responsible for varieties of neuropathogenic factors. Despite the considerable investigation of neuroprotection in curing multiple sclerosis, some complications still constrained. As of now approachable drugs give only symptomatic alleviation but don’t end the development of illness. In this way, the advancement of unused helpful techniques remains neglected restorative requires. The limitations of current steady treatment may be because of their activity at one of many neurotransmitters included or their failure to up direct signaling flag bearers detailed to have a vital part in neuronal sensitivity, biosynthesis of neurotransmitters and its discharge, development and separation of neuron, synaptic versatility and cognitive working. Therefore, the current review strictly focused on the exploration of various clinical and pre-clinical features available for multiple sclerosis to understand the pathogenic mechanisms and to introduced pharmacological interventions associated with the upregulation of intracellular adenyl cyclase/cAMP/CREB activation to ameliorate multiple sclerosis like features.

Exploring molecular approaches in Amyotrophic lateral sclerosis: Drug targets from clinical and pre-clinical findings

2020 ◽  
Vol 13 ◽  
Author(s):  
Mamtaj Alam ◽  
Rajeshwar Kumar Yadav ◽  
Elizabeth Minj ◽  
Aarti Tiwari ◽  
Sidharth Mehan
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Drug Targets ◽  
Therapeutic Index ◽  
Experimental Models ◽  
Clinical Findings ◽  
Adenyl Cyclase ◽  
Molecular Approaches ◽  
Pharmacologically Active ◽  
Lateral Sclerosis

: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease (MND) characterised by the death of upper and lower motor neurons (corticospinal tract) in the motor cortex, basal ganglia, brain stem, and spinal cord. The patient experiences the sign and symptoms between 55 to 75 years of age included impaired motor movement, difficulty in speaking and swallowing, grip loss, muscle atrophy, spasticity and sometimes associated with memory and cognitive impairments. Median survival is 3 to 5 years after diagnosis and 5 to 10% beyond 10 years of age. The limited intervention of pharmacologically active compounds that are used clinically is majorly associated with the narrow therapeutic index. Pre-clinically established experimental models where neurotoxin methyl mercury mimics the ALS like behavioural and neurochemical alterations in rodents associated with neuronal mitochondrial dysfunctions and downregulation of adenyl cyclase mediated cAMP/CREB is the main pathological hallmark for the progression of ALS in central as well in the peripheral nervous system. Despite the considerable investigation into neuroprotection, it still constrains treatment choices to strong care and organization of ALS complications. Therefore, current review specially targeted in the investigation of clinical and pre-clinical features available for ALS to understand the pathogenic mechanisms and to explore the pharmacological interventions associated with up-regulation of intracellular adenyl cyclase/cAMP/CREB and mitochondrial-ETC coenzyme-Q10 activation as a future drug target in the amelioration of ALS mediated motor neuronal dysfunctions.

Electrophysiological, Neuropsychological and Clinical Findings in Multiple Sclerosis Patients Receiving Interferon β-1b: A 1-Year Follow-Up

2000 ◽  
Vol 44 (4) ◽  
pp. 205-209 ◽  
Author(s):  
W. Gerschlager ◽  
R. Beisteiner ◽  
L. Deecke ◽  
G. Dirnberger ◽  
W. Endl ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Findings ◽  
Interferon Β ◽  
Multiple Sclerosis Patients

scholarly journals Podophyllotoxin: History, Recent Advances and Future Prospects

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 603
Author(s):  
Zinnia Shah ◽  
Umar Farooq Gohar ◽  
Iffat Jamshed ◽  
Aamir Mushtaq ◽  
Hamid Mukhtar ◽  
...  
Keyword(s):  
Structure Optimization ◽  
Cytokine Storm ◽  
Chemotherapeutic Drug ◽  
Future Prospects ◽  
Naturally Occurring ◽  
Pharmacologically Active ◽  
Almost All ◽  
Pharmacologically Active Compounds ◽  
Synthetic Derivatives ◽  
Related Compounds

Podophyllotoxin, along with its various derivatives and congeners are widely recognized as broad-spectrum pharmacologically active compounds. Etoposide, for instance, is the frontline chemotherapeutic drug used against various cancers due to its superior anticancer activity. It has recently been redeveloped for the purpose of treating cytokine storm in COVID-19 patients. Podophyllotoxin and its naturally occurring congeners have low bioavailability and almost all these initially discovered compounds cause systemic toxicity and development of drug resistance. Moreover, the production of synthetic derivatives that could suffice for the clinical limitations of these naturally occurring compounds is not economically feasible. These challenges demanded continuous devotions towards improving the druggability of these drugs and continue to seek structure-optimization strategies. The discovery of renewable sources including microbial origin for podophyllotoxin is another possible approach. This review focuses on the exigency of innovation and research required in the global R&D and pharmaceutical industry for podophyllotoxin and related compounds based on recent scientific findings and market predictions.

scholarly journals Development of A Continuous Fluorescence-Based Assay for N-Terminal Acetyltransferase D

2021 ◽  
Vol 22 (2) ◽  
pp. 594
Author(s):  
Yi-Hsun Ho ◽  
Lan Chen ◽  
Rong Huang
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
High Throughput Screening ◽  
Coenzyme A ◽  
Therapeutic Potential ◽  
Biological Functions ◽  
Histone H4 ◽  
Fluorescent Signal ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds

N-terminal acetylation catalyzed by N-terminal acetyltransferases (NATs) has various biological functions in protein regulation. N-terminal acetyltransferase D (NatD) is one of the most specific NAT with only histone H4 and H2A proteins as the known substrates. Dysregulation of NatD has been implicated in colorectal and lung cancer progression, implying its therapeutic potential in cancers. However, there is no reported inhibitor for NatD yet. To facilitate the discovery of small-molecule NatD inhibitors, we report the development of a fluorescence-based acetyltransferase assay in 384-well high-throughput screening (HTS) format through monitoring the formation of coenzyme A. The fluorescent signal is generated from the adduct in the reaction between coenzyme A and fluorescent probe ThioGlo4. The assay exhibited a Z′-factor of 0.77 and a coefficient of variation of 6%, indicating it is a robust assay for HTS. A pilot screen of 1280 pharmacologically active compounds and subsequent validation identified two hits, confirming the application of this fluorescence assay in HTS.

scholarly journals Marine-Derived Compounds with Anti-Alzheimer’s Disease Activities

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 410
Author(s):  
Salar Hafez Ghoran ◽  
Anake Kijjoa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Thinking Skills ◽  
Mechanisms Of Action ◽  
Brain Disorder ◽  
Brain Functioning ◽  
Pharmacologically Active ◽  
Pharmacologically Active Compounds

Alzheimer’s disease (AD) is an irreversible and progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to perform simple tasks. As the aging population continues to increase exponentially, AD has become a big concern for society. Therefore, neuroprotective compounds are in the spotlight, as a means to tackle this problem. On the other hand, since it is believed—in many cultures—that marine organisms in an individual diet cannot only improve brain functioning, but also slow down its dysfunction, many researchers have focused on identifying neuroprotective compounds from marine resources. The fact that the marine environment is a rich source of structurally unique and biologically and pharmacologically active compounds, with unprecedented mechanisms of action, marine macroorganisms, such as tunicates, corals, sponges, algae, as well as microorganisms, such as marine-derived bacteria, actinomycetes, and fungi, have been the target sources of these compounds. Therefore, this literature review summarizes and categorizes various classes of marine-derived compounds that are able to inhibit key enzymes involved in AD, including acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), β-secretase (BACE-1), and different kinases, together with the related pathways involved in the pathogenesis of AD. The compounds discussed herein are emerging as promising anti-AD activities for further in-depth in vitro and in vivo investigations, to gain more insight of their mechanisms of action and for the development of potential anti-AD drug leads.

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