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1.
Curr Protein Pept Sci ; 25(7): 507-526, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38561605

RESUMO

Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.


Assuntos
Doenças Neurodegenerativas , Peptídeos , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Peptídeos/uso terapêutico , Peptídeos/química , Peptídeos/farmacologia , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Doença de Huntington/tratamento farmacológico , Doença de Huntington/metabolismo , Doença de Huntington/patologia , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Inibidores da Colinesterase/uso terapêutico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química
2.
Ageing Res Rev ; 75: 101560, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35031512

RESUMO

Dementia, in particular, is a defining feature of Alzheimer's and Parkinson's diseases. Because of the combination of motor and cognitive impairments, Parkinson's disease dementia (PDD) has a greater impact on affected people than Alzheimer's disease dementia (ADD) and others. If one family member develops dementia, the other members will suffer greatly in terms of social and occupational functioning. Currently, no relevant treatment is available based on an examination of the absolute pathophysiology of dementia. As a result, our objective of current review encouraged to look for dementia pharmacotherapy based on their pathogenesis. We systematically searched electronic databases such as PubMed, Scopus, and ESCI for information on the pathophysiology of demetia, as well as their treatment with allopathic and herbal medications. By modulating intermediate proteins, oxidative stress, viral protein corona, and MMP9 are etiological factors that cause dementia. The pathophysiology of ADD was described by two hypotheses: the amyloid cascade hypothesis and the tau and tangle hypothesis. ADD is caused by an increase in amyloid-beta (Aß) and neurofibrillary tangles in the cerebrum. The viral protein corona (VPC) is more contagious and helps to form amyloid-beta (Aß) plaques and neurofibrillary tangles in the cerebrum. Thioredoxin interacting protein (TXNIP) inside the BBB encourages Aß to become more engaged. PDD is caused by decreased or absent dopamine secretion from nerve cells in the substantia nigra, as well as PRKN gene deletion/duplication mutations, and shift in the PRKN-PACRG organisation, all of which are linked to ageing. This article discussed the pathophysiology of dementia, as well as a list of herbal medications that can easily cross the BBB and have a therapeutic effect on dementia.


Assuntos
Doença de Alzheimer , Demência , Metaloproteinase 9 da Matriz , Doença de Parkinson , Coroa de Proteína , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Demência/diagnóstico , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Emaranhados Neurofibrilares/patologia , Doença de Parkinson/patologia , Proteínas Virais , Proteínas tau/metabolismo
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