The PMR1 pump in alpha-synuclein toxicity and neurodegeneration

Proteinopathies constitute a diverse group of devastating neurodegenerative disorders, characterized by aberrant aggregation of specific proteins within neurons and in the brain parenchyma. Parkinson's disease (PD) is among the most common proteinopathies, caused by the accumulation of different species of α-synuclein and the formation of protein inclusions known as Lewy bodies. Although several mutations in the α-synuclein gene have been linked to PD, the mechanisms mediating the aggregation and toxicity of α-synuclein are not fully understood. Here, we review recent evidence that highlight an intricate interplay between α-synuclein and ionostasis, focusing on the PMR1 pump, a Golgi resident Ca²⁺/Mn²⁺ P-type ATPase, which plays a pivotal role in regulating the intracellular levels of calcium and manganese ions.