Download pdf
Mechanisms and factors contributing to acetylcholine nerve cell death in Alzheimer disease
- 1 Huili School Shanghai, Shanghai, China
* Author to whom correspondence should be addressed.
Abstract
Alzheimer's disease (AD) is a severe and progressive neurodegenerative condition that is marked by a gradual deterioration of cognitive functions, leading to grievous dementia and profound functional impairment. As the disease progresses, individuals lose the ability to carry out routine tasks and daily activities, often leading to bedridden confinement and an increased risk of complications such as pneumonia. Despite considerable research efforts, the precise mechanisms underlying AD pathogenesis remain elusive. The cholinergic hypothesis, one of several proposed pathogenesis hypotheses for AD, suggests that the disease arises from the death of neurons releasing acetylcholine. This hypothesis highlights the critical role of acetylcholine in maintaining cognitive function and implies that the degeneration of these neurons contributes to the progression of AD. To better understand the mechanisms and factors contributing to acetylcholine nerve cell death in AD and how they ultimately lead to disease progression, this research aims to explore the intricate relationship between acetylcholine and AD. We examine the intricate interplay between genetic, molecular, and environmental factors that converge to promote the demise of cholinergic neurons. Ultimately, understanding the complex interplay between acetylcholine and AD pathogenesis could smooth the path for novel treatment strategies aimed at preserving neuronal function and improving patient outcomes.
Keywords
Alzheimer Disease, Acetylcholine, The Cholinergic Hypothesis, Oxidative stress, β Amyloid, Tau protein.
[1]. GBD 2016 Dementia Collaborators. Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 Jan;18(1):88-106. doi: 10.1016/S1474-4422(18)30403-4.
[2]. Dai MH, Zheng H, Zeng LD, Zhang Y. The genes associated with early-onset Alzheimer's disease. Oncotarget. 2017 Dec 15;9(19):15132-15143. doi: 10.18632/oncotarget.23738.
[3]. Hampel H, Williams C, Etcheto A, Goodsaid F, Parmentier F, Sallantin J, Kaufmann WE, Missling CU, Afshar M. A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer's disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement (N Y). 2020 Apr 19;6(1):e12013. doi: 10.1002/trc2.12013.
[4]. Chen XQ, Mobley WC. Exploring the Pathogenesis of Alzheimer Disease in Basal Forebrain Cholinergic Neurons: Converging Insights From Alternative Hypotheses. Front Neurosci. 2019 May 7;13:446. doi: 10.3389/fnins.2019.00446.
[5]. to-Mercado V, Mendivil-Perez M, Velez-Pardo C, Lopera F, Jimenez-Del-Rio M. Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer's disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications. PLoS One. 2020 May 21;15(5):e0221669. doi: 10.1371/journal.pone.0221669.
[6]. Cisterna, B.A., Vargas, A.A., Puebla, C. et al. Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation. Nat Commun 11, 1073 (2020). https://doi.org/10.1038/s41467-019-14063-8
[7]. Park HJ, Kwon H, Lee JH, Cho E, Lee YC, Moon M, Jun M, Kim DH, Jung JW. β-Amyrin Ameliorates Alzheimer's Disease-Like Aberrant Synaptic Plasticity in the Mouse Hippocampus. Biomol Ther (Seoul). 2020 Jan 1;28(1):74-82. doi: 10.4062/biomolther.2019.024.
[8]. Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, Khachaturian AS, Vergallo A, Cavedo E, Snyder PJ, Khachaturian ZS. The cholinergic system in the pathophysiology and treatment of Alzheimer's disease. Brain. 2018 Jul 1;141(7):1917-1933. doi: 10.1093/brain/awy132.
[9]. Chen ZR, Huang JB, Yang SL, Hong FF. Role of Cholinergic Signaling in Alzheimer's Disease. Molecules. 2022 Mar 10;27(6):1816. doi: 10.3390/molecules27061816.
[10]. Xu H, Garcia-Ptacek S, Jönsson L, Wimo A, Nordström P, Eriksdotter M. Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality. Neurology. 2021 Apr 27;96(17):e2220-e2230. doi: 10.1212/WNL.0000000000011832.
[11]. Sies H. Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress. Redox Biol. 2017 Apr;11:613-619. doi: 10.1016/j.redox.2016.12.035.
[12]. Forman, H.J., Zhang, H. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov 20, 689–709 (2021). https://doi.org/10.1038/s41573-021-00233-1
[13]. Aranda-Rivera AK, Cruz-Gregorio A, Aparicio-Trejo OE, Pedraza-Chaverri J. Mitochondrial Redox Signaling and Oxidative Stress in Kidney Diseases. Biomolecules. 2021 Aug 3;11(8):1144. doi: 10.3390/biom11081144.
[14]. Sharma C, Kim S, Nam Y, Jung UJ, Kim SR. Mitochondrial Dysfunction as a Driver of Cognitive Impairment in Alzheimer's Disease. Int J Mol Sci. 2021 May 3;22(9):4850. doi: 10.3390/ijms22094850.
[15]. Thadathil N, Nicklas EH, Mohammed S, Lewis TL Jr, Richardson A, Deepa SS. Necroptosis increases with age in the brain and contributes to age-related neuroinflammation. Geroscience. 2021 Oct;43(5):2345-2361. doi: 10.1007/s11357-021-00448-5.
[16]. Calvo-Rodriguez M, Bacskai BJ. Mitochondria and Calcium in Alzheimer's Disease: From Cell Signaling to Neuronal Cell Death. Trends Neurosci. 2021 Feb;44(2):136-151. doi: 10.1016/j.tins.2020.10.004.
[17]. Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE. Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 2017 Sep;38(9):1205-1235. doi: 10.1038/aps.2017.28.
[18]. Hampel, H., Hardy, J., Blennow, K. et al. The Amyloid-β Pathway in Alzheimer’s Disease. Mol Psychiatry 26, 5481–5503 (2021). https://doi.org/10.1038/s41380-021-01249-0
[19]. Haass C, Selkoe DJ. Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell. 1993 Dec 17;75(6):1039-42. doi: 10.1016/0092-8674(93)90312-e.
[20]. Ullah R, Park TJ, Huang X, Kim MO. Abnormal amyloid beta metabolism in systemic abnormalities and Alzheimer's pathology: Insights and therapeutic approaches from periphery. Ageing Res Rev. 2021 Nov;71:101451. doi: 10.1016/j.arr.2021.101451.
[21]. Chang CW, Shao E, Mucke L. Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies. Science. 2021 Feb 26;371(6532):eabb8255. doi: 10.1126/science.abb8255.
[22]. Götz J, Halliday G, Nisbet RM. Molecular Pathogenesis of the Tauopathies. Annu Rev Pathol. 2019 Jan 24;14:239-261. doi: 10.1146/annurev-pathmechdis-012418-012936.
Cite this article
Chen,J. (2024). Mechanisms and factors contributing to acetylcholine nerve cell death in Alzheimer disease. Theoretical and Natural Science,64,18-26.
Data availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
Disclaimer/Publisher's Note
The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of EWA Publishing and/or the editor(s). EWA Publishing and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.
About volume
Volume title: Proceedings of the 4th International Conference on Biological Engineering and Medical Science
© 2024 by the author(s). Licensee EWA Publishing, Oxford, UK. This article is an open access article distributed under the terms and
conditions of the Creative Commons Attribution (CC BY) license. Authors who
publish this series agree to the following terms:
1. Authors retain copyright and grant the series right of first publication with the work simultaneously licensed under a Creative Commons
Attribution License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this
series.
2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the series's published
version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial
publication in this series.
3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and
during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See
Open access policy for details).