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The role of drugs in modulating synaptic plasticity associated with aging diseases: Alzheimer’s disease
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O processo fisiológico do envelhecimento é regulado por uma variedade de mecanismos bioquímicos e genéticos, que estão intimamente ligados à longevidade e à causa de todos os distúrbios relacionados à idade. O surgimento das doenças neurodegenerativas aumenta exponencialmente com a idade, sugerindo que o cérebro é particularmente suscetível ao processo de envelhecimento (Grimm et al., 2017; Li et al., 2021).
A Organização Mundial de Saúde relata que a incidência de Alzheimer, uma das doenças neurodegenerativas associadas ao envelhecimento, está a aumentar a cada ano, levando à hipótese de que, em 2050, poderá haver três vezes mais pacientes com Alzheimer (Askarova et al., 2020).
Como o Alzheimer se destaca em número a todas as outras doenças neurodegenerativas, este será o foco principal deste manuscrito. A doença de Alzheimer começa com um estágio assintomático e evidentes biomarcadores da condição patológica. Progride expressando anormalidades cognitivas e/ou neurocomportamentais leves até atingir o estado de demência (Porsteinsson et al., 2021).
Dada a complexidade da doença, várias hipóteses etiológicas para descrever o percurso da patologia têm sido propostas, salientando-se entre elas a aglomeração de vários tipos de proteínas, que causam neuroinflamação, stress oxidativo, disfunção mitocondrial, desregulação dos sistemas enzimáticos e morte neuronal (Askarova et al., 2020).
Perturbações como as mencionadas acima causam perda sinática e neuronal e ainda neurodegeneração. O hipocampo, essencial na regulação da aprendizagem e memória, é a estrutura cerebral mais afetada pela doença de Alzheimer, tornando-o um dos principais objetos de estudo. Este exibe incrível plasticidade estrutural e funcional em resposta às mudanças ambientais, o que suscita especial interesse no combate à neurodegeneração causada pela doença (Zhang et al., 2022).
Para muitos pacientes com Alzheimer, o padrão da terapia farmacológica inclui o uso de inibidores da colinesterase e o antagonista do recetor de N-metil-D-aspartato, a memantina. A Food and Drug Administration autorizou o aducanumab, um tipo de anticorpo monoclonal humano, para tratar pacientes com Alzheimer a 7 de junho de 2021 (Scheltens et al., 2021; Vaz et al., 2022).
Devido à sua notória eficácia em reduzir drasticamente a o péptido amiloide-β no cérebro, um dos marcadores da doença de Alzheimer, o aducanumab destacou-se como o tratamento mais promissor para esta doença (Vaz et al., 2022).
Embora haja falta de mais estudos relativos à eficácia de outras terapias não farmacológicas, a terapia com células estaminais e a oxigenoterapia hiperbárica são dois potenciais candidatos para ajudar a prevenir e/ou tratar a doença de Alzheimer.
Esta dissertação foi elaborada com o objetivo de realizar uma revisão bibliográfica de artigos relacionados com a prevenção de doenças neurodegenerativas com vista em melhorar a qualidade de vida no envelhecimento, para compreender bem os mecanismos de neuroplasticidade e neurogénese e conhecer o atual estado da arte das terapêuticas e medidas preventivas existentes com a finalidade de prevenção em especial da doença de Alzheimer, que é a doença neurodegenerativa com maior impacto na população idosa.
Por fim, este manuscrito destaca a importância do diagnóstico precoce do Alzheimer, pois permite o acesso a opções de tratamento que não curam a doença, mas reduzem o declínio cognitivo e funcional em um estágio inicial da doença. Também abre novos horizontes para que as pessoas mudem o seu estilo de vida para prevenir doenças neurodegenerativas e se manterem saudáveis por mais tempo.
A pesquisa bibliográfica utilizada no presente artigo científico foi efetuada no período compreendido entre setembro de 2021 e setembro de 2022, através das bases de dados PubMed e B-On, e também entidades reguladoras da saúde como a Organização Mundial de Saúde, The National Institutes of Health e National Center for Complementary and Integrative Health.
The physiological process of aging is regulated by a variety of biochemical and genetic mechanisms, which are closely linked to longevity and the cause of all age-related disorders. The onset of neurodegenerative disorders has increased exponentially with age, suggesting that the brain is particularly susceptible to the aging process (Grimm et al., 2017; Li et al., 2021). The World Health Organization reports that the incidence of Alzheimer’s Disease (AD), a neurodegenerative disease linked to aging, is rising each year, leading to the hypothesis that by 2050, there may be three times as many Alzheimer’s patients (Askarova et al., 2020). As Alzheimer's outnumbers all other neurodegenerative diseases, it will be the main focus of this manuscript. Alzheimer's disease starts with an asymptomatic stage and biomarker evidence of the condition and progresses by expressing mild cognitive and/or neurobehavioral abnormalities until it reaches the state of dementia (Porsteinsson et al., 2021). Given the complexity of the disease several etiological hypotheses to describe the pathology course have been proposed, highlighting among them clustering several types of proteins, which cause neuroinflammation, oxidative stress, mitochondrial dysregulation of enzymatic systems and neuronal death (Askarova et al., 2020). Disturbances such as those mentioned above cause synaptic and neuronal loss as well as neurodegeneration. The hippocampus, essential in the regulation of learning and memory, is the brain structure most affected by Alzheimer's disease, making it one of the main research targets. It exhibits incredible structural and functional plasticity in response to environmental changes, which is of particular interest in combating neurodegeneration caused by the disease. (Zhang et al., 2022). For many Alzheimer's patients, the standard of pharmacological therapy includes the use of cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine. The Food and Drug Administration authorized aducanumab, a kind of human monoclonal antibody, to treat Alzheimer's patients on June 7, 2021 (Scheltens et al., 2021; Vaz et al., 2022). Due to its obvious efficacy in dramatically reducing the amyloid-β peptide in the brain, one of Alzheimer’s disease (AD)'s markers, aducanumab has emerged as the most promising treatment for AD during the past ten years (Vaz et al., 2022). Although there is a lack of further studies regarding the effectiveness of other non-pharmacological therapies, stem cell therapy and hyperbaric oxygen therapy are two potential candidates to help prevent and/or treat Alzheimer’s. This manuscript was written with the goal of conducting a literature review of articles related to the prevention of neurodegenerative diseases with a view of improving quality of life in aging, to understand well the mechanisms of neuroplasticity and neurogenesis, and know the current state of the art of existing therapies and preventive measures with the aim at preventing aging related disease in particular of Alzheimer’s disease, which is the neurodegenerative disease with the greatest impact on the elderly population. Finally, this manuscript highlights the importance of early diagnosis of AD, as it allows access to treatment options that do not cure the disease but reduce cognitive and functional decline at an early stage of the disease. It also opens new horizons for people to change their lifestyle to prevent neurodegenerative diseases and stay healthy longer. The literature search used in this manuscript was conducted between September 2021 and September 2022, using the PubMed and B-On databases, as well as health regulatory agencies such as the World Health Organization, The National Institutes of Health, and National Center for Complementary and Integrative Health.
The physiological process of aging is regulated by a variety of biochemical and genetic mechanisms, which are closely linked to longevity and the cause of all age-related disorders. The onset of neurodegenerative disorders has increased exponentially with age, suggesting that the brain is particularly susceptible to the aging process (Grimm et al., 2017; Li et al., 2021). The World Health Organization reports that the incidence of Alzheimer’s Disease (AD), a neurodegenerative disease linked to aging, is rising each year, leading to the hypothesis that by 2050, there may be three times as many Alzheimer’s patients (Askarova et al., 2020). As Alzheimer's outnumbers all other neurodegenerative diseases, it will be the main focus of this manuscript. Alzheimer's disease starts with an asymptomatic stage and biomarker evidence of the condition and progresses by expressing mild cognitive and/or neurobehavioral abnormalities until it reaches the state of dementia (Porsteinsson et al., 2021). Given the complexity of the disease several etiological hypotheses to describe the pathology course have been proposed, highlighting among them clustering several types of proteins, which cause neuroinflammation, oxidative stress, mitochondrial dysregulation of enzymatic systems and neuronal death (Askarova et al., 2020). Disturbances such as those mentioned above cause synaptic and neuronal loss as well as neurodegeneration. The hippocampus, essential in the regulation of learning and memory, is the brain structure most affected by Alzheimer's disease, making it one of the main research targets. It exhibits incredible structural and functional plasticity in response to environmental changes, which is of particular interest in combating neurodegeneration caused by the disease. (Zhang et al., 2022). For many Alzheimer's patients, the standard of pharmacological therapy includes the use of cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist memantine. The Food and Drug Administration authorized aducanumab, a kind of human monoclonal antibody, to treat Alzheimer's patients on June 7, 2021 (Scheltens et al., 2021; Vaz et al., 2022). Due to its obvious efficacy in dramatically reducing the amyloid-β peptide in the brain, one of Alzheimer’s disease (AD)'s markers, aducanumab has emerged as the most promising treatment for AD during the past ten years (Vaz et al., 2022). Although there is a lack of further studies regarding the effectiveness of other non-pharmacological therapies, stem cell therapy and hyperbaric oxygen therapy are two potential candidates to help prevent and/or treat Alzheimer’s. This manuscript was written with the goal of conducting a literature review of articles related to the prevention of neurodegenerative diseases with a view of improving quality of life in aging, to understand well the mechanisms of neuroplasticity and neurogenesis, and know the current state of the art of existing therapies and preventive measures with the aim at preventing aging related disease in particular of Alzheimer’s disease, which is the neurodegenerative disease with the greatest impact on the elderly population. Finally, this manuscript highlights the importance of early diagnosis of AD, as it allows access to treatment options that do not cure the disease but reduce cognitive and functional decline at an early stage of the disease. It also opens new horizons for people to change their lifestyle to prevent neurodegenerative diseases and stay healthy longer. The literature search used in this manuscript was conducted between September 2021 and September 2022, using the PubMed and B-On databases, as well as health regulatory agencies such as the World Health Organization, The National Institutes of Health, and National Center for Complementary and Integrative Health.
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Keywords
Neuroplasticidade Envelhecimento Fármacos Modulação sinática Doenças neurodegenerativas Alzheimer Neuroplasticity Aging Drugs Synaptic modulation Neurodegenerative diseases