Roles of αsynuclein in gastrointestinal microbiome dysbiosisrelated Parkinson's disease progression (Review).
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Are We What We Eat? Impact of Diet on the Gut–Brain Axis in Parkinson’s Disease
TL;DR: The hypothesis that Parkinson’s disease could begin in the gut is supported, with a focus on how food-based therapies might then have an influence on PD and could ameliorate non-motor as well as motor symptoms.
Journal ArticleDOI
Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis
Júlio César Claudino dos Santos,Micael Porto Portela Lima,Gerly Anne de Castro Brito,Glauce Socorro de Barros Viana +3 more
TL;DR: In this article , the authors discuss how the microbiota-gut-brain axis and environmental influences interact with the immune system to promote a pro-inflammatory state that is involved in the initiation and progression of misfolded α-synuclein proteins and the beginning of the early non-motor symptoms of Parkinson's disease.
Journal ArticleDOI
Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease
Tiantian Li,Chuanqi Chu,Leilei Yu,Qixiao Zhai,Shunhe Wang,Jianxin Zhao,Hao Zhang,Wei Jiong Chen,Fengwei Tian +8 more
TL;DR: In this paper , the effects of probiotic Bifidobacterium breve CCFM1067, administered for 5 weeks in a Parkinson's disease (PD) mouse model, were examined.
Journal ArticleDOI
Bacillus amyloliquifaciens-Supplemented Camel Milk Suppresses Neuroinflammation of Autoimmune Encephalomyelitis in a Mouse Model by Regulating Inflammatory Markers
TL;DR: In this paper , Bacillus amyloliquefaciens-supplemented camel milk (BASY) was used to assess its preventive effect on MS symptoms in a myelin oligodendrocyte glycoprotein (MOG)-immunized C57BL6J mice model.
Journal ArticleDOI
METTL14 is decreased and regulates m6A modification of α‐synuclein in Parkinson's disease
Honghu He,Qinxin Zhang,Jiajia Liao,Jiang Lei,Man Luo,Jian-feng Huang,Mei-Ling Chen,Yuefei Shen,Jing Wang,Pingyi Xu,Yousheng Xiao +10 more
TL;DR: In this article , the role of m6A modification and its underlying mechanism in Parkinson's disease was investigated and the potential of METTL14 as a novel diagnostic biomarker for PD was revealed.
References
More filters
Journal ArticleDOI
A Comparative Review of Toll-Like Receptor 4 Expression and Functionality in Different Animal Species
Céline Vaure,Yuanqing Liu +1 more
TL;DR: Current knowledge on the critical points of divergence between human and the mammalian species commonly used in vaccine research and development are focused on, in terms of molecular, cellular, and functional properties of TLR4.
Journal ArticleDOI
Inflammation as a causative factor in the aetiology of Parkinson's disease.
TL;DR: Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting mainly the elderly, although a small proportion of PD patients develop the illness at a much younger age as discussed by the authors.
Journal ArticleDOI
Dyskinesias and motor fluctuations in Parkinson's disease. A community-based study.
Anette Schrag,Niall Quinn +1 more
TL;DR: Investigation of the prevalence of dyskinesias and motor fluctuations in a community-based population of patients with Parkinson's disease concludes that motor fluctuations are most strongly related to disease duration and dose of levodopa, and dysKinesias to duration oflevodopa treatment.
Journal ArticleDOI
Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome
Erin M. Hill-Burns,Justine W. Debelius,James T. Morton,William T. Wissemann,Matthew R. Lewis,Zachary D. Wallen,Shyamal D. Peddada,Stewart A. Factor,Eric Molho,Cyrus P. Zabetian,Rob Knight,Haydeh Payami +11 more
TL;DR: There is mounting evidence for a connection between the gut and Parkinson's disease (PD).
Journal ArticleDOI
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity
Mickael Decressac,Bengt Mattsson,Pia Weikop,Martin Lundblad,Johan Jakobsson,Anders Björklund +5 more
TL;DR: It is shown that neurodegenerative changes induced by α-synuclein in midbrain dopamine neurons in vivo can be blocked through activation of the autophagy-lysosome pathway, and TFEB is identified as a promising target for therapies aimed at neuroprotection and disease modification in Parkinson disease.