Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health DOI Open Access
Valerie Uytterhoeven, Patrik Verstreken, Eliana Nachman

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(2)

Published: Dec. 24, 2024

Synaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's (PD), occurring before widespread protein aggregation, neuronal loss, cognitive decline. While field has focused on aggregation Tau α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even their aggregation. Therefore, understanding mechanisms by which α-Syn affect terminals offers an opportunity for developing innovative therapeutics aimed at preserving synapses potentially halting neurodegeneration. This review focuses molecular converge caused α-Syn. Both have physiological roles synapses. However, during disease, they acquire abnormal functions due to aberrant interactions mislocalization. We provide overview current research different essential pathways influenced Finally, we highlight promising therapeutic targets maintaining synaptic function both tauopathies synucleinopathies.

Language: Английский

Are we missing a trick by not exploiting fruit flies in inflammation-led drug discovery for neurodegeneration? DOI Creative Commons

Ray M. Price,

Miguel Ramírez Moreno, Amber Cooper

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

Alzheimer's disease (AD) remains a formidable challenge in neurodegeneration research, with limited therapeutic options despite decades of study. While Drosophila melanogaster has been instrumental modeling AD related Tau and amyloid beta toxicity, inflammation, key driver pathology, unexplored fly models. Given the evolutionary conservation innate immune pathways between flies mammals, drosophila presents powerful yet underutilized tool for inflammation led drug discovery AD. This perspective highlights relevance studying neuroinflammatory processes, including microglial-like glial activation, systemic gut-brain axis interactions. It further explores how models can be leveraged to screen anti-inflammatory compounds dissect genetic factors implicated By integrating modulation Drosophila-based pipeline we accelerate identification novel strategies. Fully exploiting potential screening may usher new era therapeutics, bridging gaps fundamental research translational medicine.

Language: Английский

Citations

0
Synaptic sabotage: How Tau and α-Synuclein undermine synaptic health DOI Open Access
Valerie Uytterhoeven, Patrik Verstreken, Eliana Nachman

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(2)

Published: Dec. 24, 2024

Synaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's (PD), occurring before widespread protein aggregation, neuronal loss, cognitive decline. While field has focused on aggregation Tau α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even their aggregation. Therefore, understanding mechanisms by which α-Syn affect terminals offers an opportunity for developing innovative therapeutics aimed at preserving synapses potentially halting neurodegeneration. This review focuses molecular converge caused α-Syn. Both have physiological roles synapses. However, during disease, they acquire abnormal functions due to aberrant interactions mislocalization. We provide overview current research different essential pathways influenced Finally, we highlight promising therapeutic targets maintaining synaptic function both tauopathies synucleinopathies.

Language: Английский

Citations

2