Roles of αsynuclein in gastrointestinal microbiome dysbiosisrelated Parkinson's disease progression (Review).
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TLDR
In this article, the abnormal accumulation of α-synuclein (α-syn) in the intestine caused by changes to the gastrointestinal microbiome (GM) caused misfolding and abnormal aggregation of α−syn in the intestines, leading to the formation of eosinophilic Lewis bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons.Abstract:
Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middle‑aged and elderly populations. Several studies have confirmed that the microbiota‑gut‑brain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of α‑synuclein (α‑syn) in the intestine. Abnormal α‑syn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of α‑syn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of α‑syn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of α‑syn in the intestine caused by the GM changes and the increased levels of α‑syn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing α‑syn accumulation to relieve the symptoms and progression of PD are described.read more
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Semi-quantitative analysis of α-synuclein in subcellular pools of rat brain neurons: An immunogold electron microscopic study using a C-terminal specific monoclonal antibody
Ling Zhang,Ling Zhang,Chunyan Zhang,Chunyan Zhang,Yuangang Zhu,Yuangang Zhu,Qing Cai,Piu Chan,Piu Chan,Kenji Uéda,Shun Yu,Shun Yu,Hui Yang,Hui Yang +13 more
TL;DR: Immunogold electron microscopy with a newly produced 3D5 monoclonal antibody recognizing the C-terminal 115-121 amino acids of alpha-Syn was used to examine its subcellular localization in rat brain neurons and showed that alpha-synuclein-positive gold particles were unevenly distributed in axons, presynaptic terminals, cytoplasm and nucleus in the neuron.