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Role of Environmental Toxicants and Inflammation in Parkinson’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Biddut Deb Nath, Dipti Debnath, Rokeya Pervin, Md. Akil Hossain
Contribution of Acetylcholine: In many neurological disorders, particularly PD and AD, acetylcholine (ACh) performs a major function in consciousness and is dysregulated. There is a large band of cell clusters inside the subventicular basal forebrain area, generally known as Meynert’s nucleus basalis (nbM), which are primarily cholinergic in function. Various kinds of neuronal impairment have been reported in nbM in patients with AD, LBD, PD, or even another types of dementia, which allows for the possibility of cholinergic system attachment in PD.79 Crucially, the involvement of LB and neuronal impairment was identified in PD cognitively impaired patients with postmortem brain tissue nbM, which indicates that the cholinergic mechanism is often implicated in the cognitive impairment recorded in PD.78
Degenerative Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James A. Mastrianni, Elizabeth A. Harris
DLB is complex and poorly understood. The features of disease are multifactorial. Motor symptoms likely result from the loss of dopamine-containing neurons within the substantia nigra, the key feature associated with PD. Cognitive dysfunction may be related to the loss of cholinergic neurons within the nucleus basalis of Meynert, as is typically present in AD. The presence of Lewy bodies in cortical layers V and VI likely impairs informational processing from neocortex to subcortical structures. Hallucinations may relate to early impairment in the parietal and occipital association cortices, which may also account for the predominance of visuospatial dysfunction in these patients compared with AD. The extreme fluctuations in alertness have not been explained.
Pre-Clinical In-Vivo and In-Vitro Methods For Evaluation of Anti-Alzheimer’s Drugs
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
Shilpa A. Deshpande, Niraj S. Vyawahare
The disruption of multiple neurotransmitter systems in AD is responsible for the pathophysiology of cognitive and behavioral disturbances associated with the disease. The majority of animal models are based on the cholinergic hypothesis of AD. Degeneration of cholinergic neurons in the nucleus basalis, situated in the basal forebrain and primarily projecting into the neocortex, occurs early in the course of the disease, resulting in cognitive impairment (Farooqui, 2016)
An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer’s disease
Published in Expert Opinion on Drug Safety, 2020
Andrea Haake, Kevin Nguyen, Lauren Friedman, Binu Chakkamparambil, George T Grossberg
Though various hypotheses have been proposed to explain the pathophysiology and symptoms of AD, including the amyloid hypothesis, hyperphosphorylated tau protein hypothesis, cholinergic deficit hypothesis, neuro-inflammation and others, current FDA-approved pharmacotherapy mostly targets the cholinergic hypothesis [6,7]. Cholinergic neurotransmitters play a very significant role in memory, learning, attention and behavior. Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) are 2 main enzymes that hydrolyze Ach in the brain [7]. The cholinergic hypothesis suggests that reduced brain acetylcholine (ACh) levels due to the atrophy of cholinergic neurons, primarily in the nucleus basalis of Meynert are the cause of cognitive decline in AD [8]. In AD, there are changes in AChE and BChE activity, which are the targets for the action of the ChEIs. Other treatment approaches targeting the amyloid and the tau hypotheses have to date not been productive including immunotherapy-based approaches, which have failed in phase II or III clinical trials [9]. With repeated failures in developing preventative and disease-modifying therapies, the Cholinesterase inhibitors (ChEIs) continue to play a pivotal role in managing the symptoms and possibly slowing the rate of progression of AD.
LC-QTOF-MS analysis of xanthone content in different parts of Garcinia mangostana and its influence on cholinesterase inhibition
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Kooi Yeong Khaw, Chun Wie Chong, Vikneswaran Murugaiyah
Severe loss of cholinergic neurons in the nucleus basalis and associated areas that form the cholinergic forebrain area resulted in up to 90% reduction in the activities of the enzyme choline acetyltransferase, which is needed for the synthesis of the neurotransmitter acetylcholine6,7. It is evident that acetylcholine, a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer’s disease as a result of reduction in its synthesis and rapid breakdown by cholinesterase enzymes8. Current available strategy for the treatment of Alzheimer's disease relies on blocking the breakdown of acetylcholine through cholinesterase inhibitors to improve brain functions, and possibly slow deteriorations of cognitive functions9. Excellent candidates from natural products are shown to improve cognitive function including Gingko biloba leaves extract, huperzine from Huperzia serrata, green tea, ginger and caffeine10–13, whereby some of them work by cholinesterase inhibition.
Recovery of an injured cingulum concurrent with improvement of short-term memory in a patient with mild traumatic brain injury
Published in Brain Injury, 2018
Sung Ho Jang, Seong Ho Kim, Jeong Pyo Seo
The cingulum, which is involved in diverse cognition, is a passage of the medial cholinergic pathway originating from the cholinergic nuclei in the basal forebrain and septal region (the medical septal nucleus [Chapter 1], the vertical nucleus of the diagonal band [Chapter 2], and the nucleus basalis of Meynert [Chapter 4], which provides cholinergic innervations to the cerebral cortex (1–3); therefore it is particularly important in memory function. Considering that cortical cholinergic activity appears to be related to short-term memory which means the ability to store new information over seconds to minutes in the cerebral cortex, the cingulum is mainly related to short-term memory function among various memory components (4–7).