Neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD) are linked to aging and lead to neuronal dysfunction and death, causing symptoms such as memory loss in AD and tremors in PD. Current treatments address only symptoms, underscoring the need to understand the mechanisms of cell death, like ferroptosis, to develop effective therapies.
Ferroptosis, a programmed cell death process driven by iron accumulation and lipid peroxidation, is relevant to neurodegeneration due to its links to oxidative stress and iron dysregulation in affected brain regions. This thesis of Nad'a Majerníková investigates ferroptosis in AD and PD through postmortem brain studies and various models, including in vitro cellular systems, 3D brain organoids, brain-on-a-chip platforms, and C. elegans.
A review of AD and ferroptosis literature highlighted the need for advanced tools and models to study ferroptosis and identify therapeutic agents. Postmortem analyses and organoid models revealed ferroptosis-related changes in AD, suggesting its involvement in disease progression and potential as a therapeutic target.
Studies in PD brains and models showed increased ferroptosis vulnerability, with α-synuclein pathology exacerbating this process. Ferroptosis inhibitors reduced cell death and toxicity, underscoring its role in PD.
Further, ferroptosis was shown to impair mitochondrial function, disrupting movement and calcium homeostasis. Healthy mitochondria transplantation rescued cells from ferroptosis-induced damage.
In conclusion, ferroptosis plays a critical role in neurodegeneration. Targeting ferroptosis, alongside related mechanisms, offers a promising therapeutic strategy for AD and PD, requiring precise approaches at appropriate disease stages.
