Avaliação do potencial da N-acetilcisteína na doença de Alzheimer
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Mar 27, 2023
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Resumo
Objetivo: Essa revisão tem como objetivo mostrar os estudos relacionados com a molécula de acetilcisteína na doença de Alzheimer, a hipótese glutamatérgica, e a mostrar diferença deste fármaco no uso de medicamentos e suplementos alimentares. Métodos: A revisão integrativa foi realizada em 6 etapas detalhados, os artigos para construção da pesquisa foram obtidos a partir das bases de dados Scopus; Scielo; MEDLINE, disponível na Universidade Federal de Paraná-UFPR, através do acesso CAFe. Pelos operadores booleanos "AND" e "OR", os termos definidos para a recolha de dados foram obtidos através dos Descritores em Ciências da Saúde (DeCS/MeSH). Resultados: Foi encontrado um total de 68 estudos, divididos entre os autores; e utilizando os critérios de inclusão e exclusão, restaram apenas 7 estudos, no qual foram adicionados à pesquisa após terem sido lidos por completo; os estudos que demonstraram melhor afinidade no uso da molécula acetilcisteina associada com Alzheimer em teste in vivo ou in vitro foram narrados na integra. Considerações finais: Na pesquisa foi possível verificar que a utilização de N-acetilcisteína off label pode ser uma molécula alvo para a doença de Alzheimer, mas para provar está ação recomenda-se a realização de mais estudos para garantir a sua eficácia.
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Como Citar
FernandesI. da C., LeiteD. R. B., de OliveiraV. D. G. S. B., DiasJ. de F. G., MontrucchioD. P., OliveiraV. B. de, DalarmiL., MiguelM. D., & MiguelO. G. (2023). Avaliação do potencial da N-acetilcisteína na doença de Alzheimer. Revista Eletrônica Acervo Saúde, 23(3), e12117. https://doi.org/10.25248/reas.e12117.2023
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32. VALLI LG. Mecanismo de ação do glutamato no sistema nervoso central e a relação com doenças neurodegenerativas. Revista Brasileira de neurologia e Psiquiatria, 2014; 18(1).
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35. KNOPMAN DS, et al. Alzheimer disease. Nature reviews Disease primers, 2021; 7(1): 33.
2. ANDERSEN JV et al. Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration. Neuropharmacology, 2021; 196: 108719.
3. BENNETT ML and VIAENE AN. What are activated and reactive glia and what is their role in neurodegeneration? Neurobiol Dis. 2021 Jan; 148:105172.
4. CZAPSKI GA and STROSZNAJDER JB. Glutamate and GABA in microglia-neuron cross-talk in Alzheimer’s disease. International Journal of Molecular Sciences, 2021; 22(21): 11677.
5. CHANG CH, et al. d-glutamate and Gut Microbiota in Alzheimer's Disease. Int J Mol Sci., 2020; 21(8): 2676.
6. DUXIN SUN, et al. Why 90% of clinical drug development fails and how to improve it?, Acta Pharmaceutica Sinica B, 2022; 12(7): 3049-3062.
7. ERCOLE FF, et al. Revisão integrativa versus revisão sistemática. Revista Mineira de Enfermagem, 2014; 18(1): 9-12.
8. FORUM. Forum on Neuroscience and Nervous System Disorders; Board on Health Sciences Policy; Institute of Medicine. Improving and Accelerating Therapeutic Development for Nervous System Disorders: Workshop Summary. Washington (DC): National Academies Press (US); 2014 Feb 6. 2, Drug Development Challenges. Available from: https://www.ncbi.nlm.nih.gov/books/NBK195047/.
9. GOV. Suplementos alimentares. 16 de outubro de 2020. Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/alimentos/suplementos-alimentares#:~:text=O%20que%20%C3%A9%20um%20suplemento,probi%C3%B3ticos%20em%20complemento%20%C3%A0%20alimenta%C3%A7%C3%A3o.
10. HSIAO YH, et al. Amelioration of social isolation-triggered onset of early Alzheimer's disease-related cognitive deficit by N-acetylcysteine in a transgenic mouse model. Neurobiol Dis., 2012; 45(3): 1111-20.
11. HYND MR, et al. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease. Neurochem Int., 2004; 45(5): 583-95.
12. JOHNSON JW and KOTERMANSKI SE. Mechanism of action of memantine. Curr Opin Pharmacol., 2006; 6(1): 61-7.
13. KOIDE K, et al. The Use of 3,5,4'-Tri-O-acetylresveratrol as a Potential Pro-drug for Resveratrol Protects Mice from γ-Irradiation-Induced Death. ACS Med Chem Lett., 2011; 2(4): 270-274.
14. MDSYSTEMS. The Glutamatergic System in Alzheimer's Disease. (S.d) Disponível em: https://www.rndsystems.com/research-area/the-glutamatergic-system-in-alzheimer-s-disease#:~:text=The%20glutamatergic%20hypothesis%20postulates%20that,pathological%20increase%20in%20intracellular%20calcium. Acessed: Sept. 12, 2022.
15. MORE J, et al. N-Acetylcysteine Prevents the Spatial Memory Deficits and the Redox-Dependent RyR2 Decrease Displayed by an Alzheimer's Disease Rat Model. Front Aging Neurosci., 2018; 10: 399.
16. NABUCO HCG, et al. Fatores associados ao uso de suplementos alimentares entre atletas: revisão sistemática. Revista Brasileira de Medicina do Esporte, 2016; 22: 412-419.
17. NEELY MD, et al. Congeners of N(alpha)-acetyl-L-cysteine but not aminoguanidine act as neuroprotectants from the lipid peroxidation product 4-hydroxy-2-nonenal. Free Radic Biol Med., 2000; 29(10): 1028-36.
18. NORTH BJ and VERDIN E. Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol., 2004; 5(5): 224.
19. OOI SL, et al. N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence. Biomed Res Int., 2018; 2018: 2469486.
20. PENUGONDA S and ERCAL N. Comparative evaluation of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) on glutamate and lead-induced toxicity in CD-1 mice. Toxicol Lett., 2011; 201(1): 1-7.
21. PLANALTO. Legislação no 6.360, de 23 de setembro de 1976. Disponível em: http://www.planalto.gov.br/ccivil_03/leis/l6360.htm. Acessed: Oct. 2, 2022.
22. PUBCHEM. National Center for Biotechnology Information. PubChem Compound Summary for CID 12035, Acetylcysteine. Disponível em: https://pubchem.ncbi.nlm.nih.gov/compound/Acetylcysteine. Acessed: Oct. 2, 2022.
23. PUBCHEM. National Center for Biotechnology Information. "PubChem Compound Summary for CID 5862, Cysteine" PubChem. Disponível em: https://pubchem.ncbi.nlm.nih.gov/compound/Cysteine. Acessed: Oct. 24, 2022.
24. RAGHU G, et al. The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress. Curr Neuropharmacol., 2021; 19(8): 1202-1224.
25. ROBINSON RA, et al. Proteomic analysis of brain proteins in APP/PS-1 human double mutant knock-in mice with increasing amyloid β-peptide deposition: insights into the effects of in vivo treatment with N-acetylcysteine as a potential therapeutic intervention in mild cognitive impairment and Alzheimer's disease. Proteomics, 2011; 11(21): 4243-56.
26. VAN HECKE O and LEE J. Disponível em: https://www.cebm.net/covid-19/n-acetylcysteine-a-rapid-review-of-the-evidence-for-effectiveness-in-treating-covid-19/.Acess in: 12 oct. 2022.
27. SAUDE. Portaria nº 344, de 12 de maio de 1998. Disponível em https://bvsms.saude.gov.br/bvs/saudelegis/svs/1998/prt0344_12_05_1998_rep.html. Acessed: Oct. 2, 2022.
28. SCRIABINE A and RABIN DU. New developments in the therapy of pulmonary fibrosis. Adv Pharmacol., 2009; 57: 419-64.
29. SLATTERY J, et al. Clinical trials of N-acetylcysteine in psychiatry and neurology: a systematic review. Neuroscience & Biobehavioral Reviews, 2015; 55: 294-321.
30. SHAHIDI S, et al. Influence of N-acetyl cysteine on beta-amyloid-induced Alzheimer’s disease in a rat model: A behavioral and electrophysiological study. Brain research bulletin, 2017; 131: 142-149.
31. TARDIOLO G, et al. Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules, 2018; 23(12): 3305.
32. VALLI LG. Mecanismo de ação do glutamato no sistema nervoso central e a relação com doenças neurodegenerativas. Revista Brasileira de neurologia e Psiquiatria, 2014; 18(1).
33. ZHANG D, et al. Opposite in vivo effects of agents that stimulate or inhibit the glutamate/cysteine exchanger system xc- on the inhibition of hippocampal LTP by Aß. Hippocampus, 2016; 26(12): 1655-1665.
34. FALCO AD, et al. Doença de alzheimer: hipóteses etiológicas e perspectivas de tratamento. Química Nova, 2016; 39(1).
35. KNOPMAN DS, et al. Alzheimer disease. Nature reviews Disease primers, 2021; 7(1): 33.