α-Synuclein is a presynaptic neuronal protein linked to Parkinson's disease (PD) and other neurodegenerative conditions called synucleinopathies. Aberrant forms of α-synuclein, such as protofibrils, are thought to be toxic and contribute to neuronal death by disrupting cellular homeostasis. Secreted α-synuclein can also seed aggregation, potentially spreading the disease. Genetic studies have shown that mutations in the SNCA gene, which encodes α-synuclein, are associated with both familial and sporadic PD. These mutations include point mutations like A53T, A30P, and E46K, as well as triplications of the SNCA locus. α-Synuclein is also found in other synucleinopathies, such as multiple-system atrophy (MSA) and dementia with Lewy bodies (DLB). α-Synuclein pathology is widespread in PD and related disorders, with a distinct pattern of distribution in different brain regions. It is found in Lewy bodies (LBs) and in neuritic processes, and its presence is a key feature in the neuropathological diagnosis of PD. α-Synuclein is a natively unfolded protein that can form α-helical or β-sheet structures upon binding to lipids or prolonged incubation. It is involved in synaptic function, neurotransmitter release, and may modulate synaptic transmission. α-Synuclein is also involved in protein degradation pathways, including autophagy and the proteasome. Aberrant α-synuclein can impair these pathways, leading to the accumulation of toxic species. α-Synuclein can also interact with other proteins, such as synphilin-1, and may contribute to neurodegeneration. α-Synuclein is found in the nucleus and can interact with histones, affecting histone acetylation. α-Synuclein can be secreted and may propagate pathology by seeding aggregation in neighboring cells. The role of α-synuclein in PD is complex, involving both genetic and environmental factors, and it is a key target for therapeutic strategies in PD and other synucleinopathies.α-Synuclein is a presynaptic neuronal protein linked to Parkinson's disease (PD) and other neurodegenerative conditions called synucleinopathies. Aberrant forms of α-synuclein, such as protofibrils, are thought to be toxic and contribute to neuronal death by disrupting cellular homeostasis. Secreted α-synuclein can also seed aggregation, potentially spreading the disease. Genetic studies have shown that mutations in the SNCA gene, which encodes α-synuclein, are associated with both familial and sporadic PD. These mutations include point mutations like A53T, A30P, and E46K, as well as triplications of the SNCA locus. α-Synuclein is also found in other synucleinopathies, such as multiple-system atrophy (MSA) and dementia with Lewy bodies (DLB). α-Synuclein pathology is widespread in PD and related disorders, with a distinct pattern of distribution in different brain regions. It is found in Lewy bodies (LBs) and in neuritic processes, and its presence is a key feature in the neuropathological diagnosis of PD. α-Synuclein is a natively unfolded protein that can form α-helical or β-sheet structures upon binding to lipids or prolonged incubation. It is involved in synaptic function, neurotransmitter release, and may modulate synaptic transmission. α-Synuclein is also involved in protein degradation pathways, including autophagy and the proteasome. Aberrant α-synuclein can impair these pathways, leading to the accumulation of toxic species. α-Synuclein can also interact with other proteins, such as synphilin-1, and may contribute to neurodegeneration. α-Synuclein is found in the nucleus and can interact with histones, affecting histone acetylation. α-Synuclein can be secreted and may propagate pathology by seeding aggregation in neighboring cells. The role of α-synuclein in PD is complex, involving both genetic and environmental factors, and it is a key target for therapeutic strategies in PD and other synucleinopathies.