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Research Advantages in Marine Microbial Acetylcholinesterase Inhibitors Against Alzheimer’S Disease: an Overview Sneha Sabu1 and A

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Research Advantages in Marine Microbial Acetylcholinesterase Inhibitors Against Alzheimer’S Disease: an Overview Sneha Sabu1 and A ISSN (Online) 2581-9429 IJAR SCT ISSN (Print) 2581-XXXX International Journal of Advanced Research in Science, Communication and Technology (IJARSCT) Volume 1, Issue 2, January 2021 Impact Factor: 4.819 Research Advantages in Marine Microbial Acetylcholinesterase Inhibitors Against Alzheimer’s Disease: An Overview Sneha Sabu1 and A. Jothilin Subitsha2 M.Sc., Department of Microbiology Centre for Marine Science & Technology, Manonmaniam Sundaranar University, Rajakamangalam, Kanyakumari, Tamil Nadu, India Abstract: Public health is significantly threatened by neurodegenerative disorders, especially Alzheimer's disease (AD). A significant cause of dementia is Alzheimer's disease (AD), accounting for up to 75 percent of all cases of dementia. Degeneration of neurons and synapses, primarily characterized by cholinergic dysfunction, are the pathophysiological processes defined for AD progression. This function makes inhibitors of acetylcholinesterase (AChEi) the main class of drugs commonly used to treat the dementia process of AD. The symptomatic progress of Alzheimer's disease (AD) remains a highly viable target since the cholinergic deficiency is a clear and early finding in AD. More and more marine compounds have been isolated from marine animals for the medicinal treatment of neurological conditions, including Alzheimer's disease (AD). Significant producers of AChEIs are fungi and bacteria. Alkaloids, terpenoids, phenylpropanoids, and steroids are the active components in fermentation products. In this review, we provide an overview of the different marine microbe-derived AChEIs and their producing strains. Keywords: Alzheimer’s Disease, Acetylcholinesterase, Acetylcholinesterase inhibitors, Marine Microorganisms, Microbial AChEI compounds. I. INTRODUCTION Alzheimer's disease (AD) is a neurodegenerative disease that can be characterized by the presence of amyloid plaques, neurofibrillary tangles, neuroinflammation, elevated oxidative stress levels and a substantial decrease in acetylcholine concentrations (ACh) [1]. It is a significant cause of dementia, responsible for up to 75% of all cases of dementia, and has become a population-ageing problem for governments and public health systems around the world due to its direct and indirect costs [2,3,4]. It has been predicted that by the year2050, one in every 85 individuals will suffer from AD [5,6]. This disorder is potrayed by the progressive irreversible loss of neurons in specific brain areas, mainly the hippocampus, accumulation of β-amyloid protein (Aβ) plaques and neurofibrillary tangles (NFTs) in brain tissues, hyperphosphorylation of Tau protein in neurons, and collapsing of cognitive functions leading to death [7,8]. Oxidative stress and the formation of reactive oxygen species (ROS) are viewed as the primary driver of this disease [9]. An important approach to treat AD is directed to the inhibition of acetylcholinesterase (AchE). Inhibitors of acetylcholinesterase (AChE) are chemical compounds that have been found to be one of the most therapeutic instruments for several neurodegenerative conditions such as Alzheimer's disease (AD), glaucoma, Parkinson's disease, myasthenia gravity, and Down syndrome. Inhibitors of acetylcholinesterase (AChE) could rebalance the acetylcholine level by inhibiting the activity of AChE. Acetylcholine could therefore accumulate in the synaptic cleft [10]. This route is called the cholinergic approach and is considered themajor symptomatic treatment for AD. However, it is difficult to underestimate the value of acetylcholinesterase inhibitors because recent research shows that these inhibitors protect brain cells from free radical damage and β-amyloid toxicity in Alzheimer’s disease (AD) [11]. Copyright to IJARCST DOI: 10.48175/IJARSCT-733 123 www.ijarsct.co.in ISSN (Online) 2581-9429 IJAR SCT ISSN (Print) 2581-XXXX International Journal of Advanced Research in Science, Communication and Technology (IJARSCT) Volume 1, Issue 2, January 2021 Impact Factor: 4.819 Researchers around the world are still searching for new sources of AChE inhibitors, amid the hunt for new medicines to avoid, delay or prevent AD, because of the concerns about bioavailability and side effects problems associated with the latest, mainly generic, drugs for AD. AChE inhibitors can be obtained either by chemical synthesis or by natural plant extraction and microorganisms. Most AChE inhibitors are plant-based [12,13], but they have also been isolated from algae extracts, fungi, cyanobacteria, marine phytoplankton and marine sessile species, such as sponges and soft corals. Because of its advantages over both phytoextraction and chemical synthesis, microbial development of AChE inhibitors is gaining a lot of attention. On the one hand, due to excessive harvesting, extraction methods are constrained by the lack of natural plant resources, and chemical synthesis threatens the environment through contamination and hazardous materials [14]. Marked-available plant-based AChE inhibitors and chemical synthesis, on the other hand, have shown many drawbacks, such as poor bioavailability and other abdominal side effects [15]. It is therefore a must to investigate other alternatives to AChE inhibitors derived from microbial sources with distinct niches. We set out to study the prevalence of acetylcholinesterase inhibitors in marine bacteria and fungi, coonsidering the immense diversity of marine microorganisms. This review gathers information on marine microorganisms that are known to be promising producers of anti-AD drugs that have demonstrated anti-AChE efficacy. II. ALZHEIMER’S DISEASE (AD) The most common neurodegenerative condition is Alzheimer's disease (AD), with symptoms that usually include confusion, lack of memory, diminished cognitive and emotional function, and dementia. It is a major cause of dementia, accounting for up to 75 percent of all dementia cases, and has become an inhabitant’s aging-related concern for policymakers and public health systems around the world by its both direct and indirect costs [16,17,4]. These days, AD pervasiveness among people over 60 years old is approximated at 40.2 per1000, while its prevalence proportion is 34.1 per 1,000[17,18]. Those percentages indicate that over a 45million people are suffering from Alzheimer’s disease worldwide, whereas this situation is expected to double every 20 years until at least 2050 [4]. Progressive neurodegenerative disorder, clinically evidenced by cognitive and memory loss, progressive deterioration in everyday activities, and some neuropsychiatric symptoms and behavioral disorders, are primarily defined by AD.Woefully,no drug can successfully reverse the injury and mortality caused by AD, a severe threat to global public health that is believed to be a complex disease with various pathological factors [18]. A meta-analysis of data sets collected between 1980 and 2009 predicts a rising prevalence of cases of global dementia; from 65.7 million in 2030 to 115.4 million in2050 [19]. In AD, brain cholinergic neurons accumulate phosphorylated microtubule-associated proteins (Tau), [20] aggregated amyloid-beta (Ab) peptides that form senile plaques and display increased AChE activity at the early stages of the disease. These processes contribute to the deficiency of acetylcholine and the progressive loss of cognitive function affecting brain neurons. In addition to issues of orientation, perception, learning, and other cognitive skills that impair the capacity of individuals to perform everyday tasks effectively, neuron degeneration is expressed in memory loss. Neurofibrillary tangles, one of the main hallmarks of AD, may form hyperphosphorylated tau. In addition, free radicals can cause oxidative stress in the AD brain and result in neuronal degeneration [21,22]. Acetylcholinesterase (AChE) plays a critical part in cholinergic transmission through the hydrolysis of the neurotransmitter acetylcholine.It is commonly recognized that the dysfunction of the cholinergic system, such as the enhancement of AChE activity and the decline of choline acetyltransferase (ChAT) level in brains, is the primary cause leading to cognitive impairments in AD patients [23]. III. ACETYLCHOLINESTERASE INHIBITORS A key enzyme responsible for the hydrolysis of acetylcholine (ACh) during cholinergic synapses into choline and acetate is acetylcholinesterase. In many vertebrates and insects, AChE is involved in nerve transmission, where both the three-dimensional structure and the enzyme's amino acid active site sequence are highly conserved [24]. Up to 5000 acetylcholine molecules per second can be hydrolyzed by each AChE enzyme, thus operating near the diffusion rate [25]. In the vertebrate cholinergic pathways in the brain, skeletal muscle, and the autonomous nervous system, the main Copyright to IJARCST DOI: 10.48175/IJARSCT-733 124 www.ijarsct.co.in ISSN (Online) 2581-9429 IJAR SCT ISSN (Print) 2581-XXXX International Journal of Advanced Research in Science, Communication and Technology (IJARSCT) Volume 1, Issue 2, January 2021 Impact Factor: 4.819 function of AChE is to regulate neurotransmission. AChE is typically discovered through a glycosylphos- phatidylinositol anchor as an amphiphilic tetramer associated with the plasma membrane in the synaptic cleft, but may also exist as a free enzyme [25,26]. Mechanism of AChE action in neurotransmission is shown in fig 1 Figure 1: Mechanism of AChE Action in Neurotransmission Inhibitors of acetylcholinesterase (AChE) are chemical compounds that are regarded as one of the most
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