α-Synuclein is the major pathological component of synucleinopathies including Parkinson's disease and dementia with Lewy bodies. Recent studies have demonstrated that α-synuclein also plays important roles in the release of synaptic vesicles and synaptic membrane recycling in healthy neurons. However, the precise relationship between the pathogenicity and physiological functions of α-synuclein remains to be elucidated. To address this issue, we investigated the subcellular localization of α-synuclein in normal and pathological conditions using primary mouse hippocampal neuronal cultures. While some neurons expressed high levels of α-synuclein in presynaptic boutons and cell bodies, other neurons either did not or only very weakly expressed the protein. These α-synuclein-negative cells were identified as inhibitory neurons by immunostaining with specific antibodies against glutamic acid decarboxylase (GAD), parvalbumin, and somatostatin. In contrast, α-synuclein-positive synapses were colocalized with the excitatory synapse marker vesicular glutamate transporter-1. This expression profile of α-synuclein was conserved in the hippocampus in vivo. In addition, we found that while presynaptic α-synuclein colocalizes with synapsin, a marker of presynaptic vesicles, it is not essential for activity-dependent membrane recycling induced by high potassium treatment. Exogenous supply of preformed fibrils generated by recombinant α-synuclein was shown to promote the formation of Lewy body (LB) -like intracellular aggregates involving endogenous α-synuclein. GAD-positive neurons did not form LB-like aggregates following treatment with preformed fibrils, however, exogenous expression of human α-synuclein allowed intracellular aggregate formation in these cells. These results suggest the presence of a different mechanism for regulation of the expression of α-synuclein between excitatory and inhibitory neurons. Furthermore, α-synuclein expression levels may determine the efficiency of intracellular aggregate formation in different neuronal subtypes.
α - Synuclein is the major pathological component of synucleinopathies including Parkinson 's disease and dementia with Lewy bodies . Recent studies have demonstrated that α - synuclein also plays important roles in the release of synaptic vesicles and synaptic membrane recycling in healthy neurons . However , the precise relationship between the pathogenicity and physiological functions of α - synuclein remains to be elucidated . To address this issue , we investigated the subcellular localization of α - synuclein in normal and pathological conditions using primary mouse hippocampal neuronal cultures . While some neurons expressed high levels of α - synuclein in presynaptic boutons and cell bodies , other neurons either did not or only very weakly expressed the protein . These α - synuclein - negative cells were identified as inhibitory neurons by immunostaining with specific antibodies against glutamic acid decarboxylase ( GAD ) , parvalbumin , and somatostatin . In contrast , α - synuclein - positive synapses were colocalized with the excitatory synapse marker vesicular glutamate transporter-1 . This expression profile of α - synuclein was conserved in the hippocampus in vivo . In addition , we found that while presynaptic α - synuclein colocalizes with synapsin , a marker of presynaptic vesicles , it is not essential for activity - dependent membrane recycling induced by high potassium treatment . Exogenous supply of preformed fibrils generated by recombinant α - synuclein was shown to promote the formation of Lewy body ( LB ) -like intracellular aggregates involving endogenous α - synuclein . GAD - positive neurons did not form LB - like aggregates following treatment with preformed fibrils , however , exogenous expression of human α - synuclein allowed intracellular aggregate formation in these cells . These results suggest the presence of a different mechanism for regulation of the expression of α - synuclein between excitatory and inhibitory neurons . Furthermore , α - synuclein expression levels may determine the efficiency of intracellular aggregate formation in different neuronal subtypes .
Which is the primary protein component of Lewy bodies?
Which is the primary protein component of Lewy bodies ?
α-synuclein
alpha-synuclein α-synuclein αSyn