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Article: Unravelling the mechanotransduction pathways in Alzheimer's disease.

Donnaloja, Francesca / Limonta, Emma / Mancosu, Christian / Morandi, Francesco / Boeri, Lucia / Albani, Diego / Raimondi, Manuela Teresa

Journal of biological engineering

2023  Volume 17, Issue 1, Page(s) 22

Abstract: Alzheimer's disease (AD) represents one of the most common and debilitating neurodegenerative disorders. By the end of 2040, AD patients might reach 11.2 million in the USA, around 70% higher than 2022, with severe consequences on the society. As now, we ...

Abstract Alzheimer's disease (AD) represents one of the most common and debilitating neurodegenerative disorders. By the end of 2040, AD patients might reach 11.2 million in the USA, around 70% higher than 2022, with severe consequences on the society. As now, we still need research to find effective methods to treat AD. Most studies focused on the tau and amyloid hypothesis, but many other factors are likely involved in the pathophysiology of AD. In this review, we summarize scientific evidence dealing with the mechanotransduction players in AD to highlight the most relevant mechano-responsive elements that play a role in AD pathophysiology. We focused on the AD-related role of extracellular matrix (ECM), nuclear lamina, nuclear transport and synaptic activity. The literature supports that ECM alteration causes the lamin A increment in the AD patients, leading to the formation of nuclear blebs and invaginations. Nuclear blebs have consequences on the nuclear pore complexes, impairing nucleo-cytoplasmic transport. This may result in tau hyperphosphorylation and its consequent self-aggregation in tangles, which impairs the neurotransmitters transport. It all exacerbates in synaptic transmission impairment, leading to the characteristic AD patient's memory loss. Here we related for the first time all the evidence associating the mechanotransduction pathway with neurons. In addition, we highlighted the entire pathway influencing neurodegenerative diseases, paving the way for new research perspectives in the context of AD and related pathologies.
Language English
Publishing date 2023-03-28
Publishing country England
Document type Journal Article ; Review
ZDB-ID 2391582-1
ISSN 1754-1611
ISSN 1754-1611
DOI 10.1186/s13036-023-00336-w
Database MEDical Literature Analysis and Retrieval System OnLINE

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