TY  - JOUR
IS  - 1
Y1  - 2024///
SN  - 2058-7716
ID  - publicatio34222
EP  - 10
TI  - Mechanism of motoneuronal and pyramidal cell death in amyotrophic lateral sclerosis and its potential therapeutic modulation
AV  - public
UR  - https://doi.org/10.1038/s41420-024-02055-7
VL  - 10
A1  -  Nógrádi Bernát
A1  -  Nógrádi-Halmi Dóra
A1  -  Erdélyi-Furka Barbara Fanni
A1  -  Kádár Zalán
A1  -  Csont Tamás Bálint
A1  -  Molnár-Gáspár Renáta
JF  - CELL DEATH DISCOVERY
N2  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder clinically characterized by muscle atrophy and progressive paralysis. Loss of motoneurons and pyramidal cells is thought to be the center piece of the complex and multifaceted ALS pathology, however, the exact mechanisms laying behind motoneuronal cell death in the spinal cord and motor cortex are still unknown. It was originally proposed that apoptosis plays a fundamental role in motoneuronal demise, nonetheless, later it became clear that other forms of regulated cell death, including necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death, may also contribute to motoneuron loss. Over the past years, multiple studies aimed to improve our understanding of the contributory role of these mechanisms as well as to offer novel targets for potential therapeutic interventions. The pharmacological inhibition of the ferroptotic pathway and the modulation of the autophagic machinery seem to have particularly promising effects, reducing motoneuron loss and slowing disease progression in transgenic models of ALS. Nevertheless, the potential beneficial effects of necroptosis-targeting interventions were mostly disproven in the latest studies. In this review we aim to summarize the current view on regulated cell death mechanisms that lead to motoneuronal and pyramidal cell degeneration in ALS and showcase their applicability as future drug targets.
ER  -