Fronza_2023_Ageing.Res.Rev__102033

Reference

Title : The Neurobiology and Therapeutic Potential of Multi-Targeting beta-secretase, Glycogen Synthase Kinase 3beta and Acetylcholinesterase in Alzheimer's Disease - Fronza_2023_Ageing.Res.Rev__102033
Author(s) : Fronza MG , Alves D , Pratico D , Savegnago L
Ref : Ageing Res Rev , :102033 , 2023
Abstract :

Alzheimer's Disease (AD) is the most common form of dementia, affecting almost 50 million of people around the world, characterized by a complex and age-related progressive pathology with projections to duplicate its incidence by the end of 2050. AD pathology has two major hallmarks, the amyloid beta (Abeta) peptides accumulation and tau hyperphosphorylation, alongside with several sub pathologies including neuroinflammation, oxidative stress, loss of neurogenesis and synaptic dysfunction. In recent years, extensive research pointed out several therapeutic targets which have shown promising effects on modifying the course of the disease in preclinical models of AD but with substantial failure when transposed to clinic trials, suggesting that modulating just an isolated feature of the pathology might not be sufficient to improve brain function and enhance cognition. In line with this, there is a growing consensus that an ideal disease modifying drug should address more than one feature of the pathology. Considering these evidence, beta-secretase (BACE1), Glycogen synthase kinase 3beta (GSK-3beta) and acetylcholinesterase (AChE) has emerged as interesting therapeutic targets. BACE1 is the rate-limiting step in the Abeta production, GSK-3beta is considered the main kinase responsible for Tau hyperphosphorylation, and AChE play an important role in modulating memory formation and learning. However, the effects underlying the modulation of these enzymes are not limited by its primarily functions, showing interesting effects in a wide range of impaired events secondary to AD pathology. In this sense, this review will summarize the involvement of BACE1, GSK-3beta and AChE on synaptic function, neuroplasticity, neuroinflammation and oxidative stress. Additionally, we will present and discuss new perspectives on the modulation of these pathways on AD pathology and future directions on the development of drugs that concomitantly target these enzymes.

PubMedSearch : Fronza_2023_Ageing.Res.Rev__102033
PubMedID: 37595640

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Citations formats

Fronza MG, Alves D, Pratico D, Savegnago L (2023)
The Neurobiology and Therapeutic Potential of Multi-Targeting beta-secretase, Glycogen Synthase Kinase 3beta and Acetylcholinesterase in Alzheimer's Disease
Ageing Res Rev :102033

Fronza MG, Alves D, Pratico D, Savegnago L (2023)
Ageing Res Rev :102033