# From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae

## TL;DR

This paper reviews how baker's yeast is used to study and find treatments for neurodegenerative diseases like Parkinson's and Alzheimer's.

## Contribution

The paper highlights the development and application of yeast models expressing human disease-related proteins for drug discovery.

## Key findings

- Yeast models expressing human proteins like amyloid-β and α-synuclein help identify drug candidates for neurodegenerative diseases.
- These models reveal conserved pathways in mammalian systems, aiding in understanding disease mechanisms.
- Yeast-based drug screening has uncovered key factors involved in protein metabolism and toxicity.

## Abstract

Here, we review the use of Saccharomyces cerevisiae as a powerful model organism for studying cellular processes implicated in neurodegenerative disorders, including stress responses, proteostasis impairment, and vesicle trafficking defects. Over the last two decades, baker's yeast models have been developed for complex diseases such as Parkinson's, Alzheimer's, Huntington's, and Amyotrophic lateral sclerosis (ALS). Yeast cells expressing human proteins, such as amyloid‐β, α‐synuclein, huntingtin, and TDP‐43, have become crucial tools for high‐throughput drug screening aimed at counteracting disease progression. These yeast models have unveiled key components involved in the metabolism and toxicity of these proteins, enabling the identification of interacting partners and novel factors within each pathway. Importantly, these pathways were subsequently shown to be conserved in mammalian models. Furthermore, drug candidates identified using yeast models have provided significant leads for drug discovery, highlighting their potential for developing treatments for these neurodegenerative diseases.

Yeast plasmids expressing human Aβ‐42, α‐syn, htt, and TDP‐43. Their fate includes an equilibrium between the endocytic pathway and aggregates that potentially disrupt endocytosis, vesicular transport, vacuolar autophagy, and mitochondrial activity.

Yeast models help find treatments for brain diseases.

Yeast models help find treatments for brain diseases.