Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

• Autor(a) principal: Cruz-Vicente, Pedro
• Data de Publicação: 2021
• Outros Autores: Passarinha, Luís A., Silvestre, Samuel Martins, Gallardo, Eugenia
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/105254; https://doi.org/10.3390/molecules26082193
• topic: neurodegenerative diseases; Parkinson’s Disease; Alzheimer’s Disease; computer-aided drug design; in silico studies; Acetylcholinesterase; Alzheimer Disease; Amyloid Precursor Protein Secretases; Antiparkinson Agents; Aspartic Acid Endopeptidases; Catechol O-Methyltransferase; Cholinesterase Inhibitors; Clinical Trials as Topic; Computer Simulation; Dopamine Agents; Drug Design; Excitatory Amino Acid Antagonists; GPI-Linked Proteins; Gene Expression Regulation; Humans; Neuroprotective Agents; Parkinson Disease; Receptors, N-Methyl-D-Aspartate; Sirtuins

Neurodegenerative diseases (ND), including Alzheimer's (AD) and Parkinson's Disease (PD), are becoming increasingly more common and are recognized as a social problem in modern societies. These disorders are characterized by a progressive neurodegeneration and are considered one of the main causes of disability and mortality worldwide. Currently, there is no existing cure for AD nor PD and the clinically used drugs aim only at symptomatic relief, and are not capable of stopping neurodegeneration. Over the last years, several drug candidates reached clinical trials phases, but they were suspended, mainly because of the unsatisfactory pharmacological benefits. Recently, the number of compounds developed using in silico approaches has been increasing at a promising rate, mainly evaluating the affinity for several macromolecular targets and applying filters to exclude compounds with potentially unfavorable pharmacokinetics. Thus, in this review, an overview of the current therapeutics in use for these two ND, the main targets in drug development, and the primary studies published in the last five years that used in silico approaches to design novel drug candidates for AD and PD treatment will be presented. In addition, future perspectives for the treatment of these ND will also be briefly discussed.