Akkermansia muciniphila induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine cell line

Neto, Dionísio Pedro Amorim; Bosque, Beatriz Pelegrini; Godoy, João Vitor Pereira de; Rodrigues, Paulla Vieira; Meneses, Dario Donoso; Tostes, Katiane; Tonoli, C.C.C.; Carvalho, Hernandes F.; González-Billault, Christian; Fonseca, Matheus de Castro

doi:10.1016/j.isci.2022.103908

Cited by 40 publications

(29 citation statements)

References 117 publications

(148 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In transgenic mouse models of PD, the gut microbiota promotes pathological alpha-synuclein accumulation, neuroinflammation, and dopaminergic neuronal degeneration, along with aggravation of motor and non-motor symptoms, which were alleviated in germ-free conditions [ 113 ]. In addition, recent research has shown that Akkermansia induces intestinal alpha-synuclein aggregation as a result of mitochondrial calcium overload in intestinal enteroendocrine cells, which were hypothesized to be an initiating site for alpha-synucleinopathy in response to environmental factors because they are connected to enteric nerves and found to have adjacent accumulation of alpha-synuclein proteins [ 118 , 119 ].…”

Section: Metagenomic and Metabolomic Evidence Of Gastrointestinal Inv...mentioning

confidence: 99%

Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis

Chen

Lin

2022

J Biomed Sci

View full text Add to dashboard Cite

Parkinson’s disease (PD) is the second most common neurodegenerative disease attributed to the synergistic effects of genetic risk and environmental stimuli. Although PD is characterized by motor dysfunction resulting from intraneuronal alpha-synuclein accumulations, termed Lewy bodies, and dopaminergic neuronal degeneration in the substantia nigra, multiple systems are involved in the disease process, resulting in heterogenous clinical presentation and progression. Genetic predisposition to PD regarding aberrant immune responses, abnormal protein aggregation, autophagolysosomal impairment, and mitochondrial dysfunction leads to vulnerable neurons that are sensitive to environmental triggers and, together, result in neuronal degeneration. Neuropathology studies have shown that, at least in some patients, Lewy bodies start from the enteric nervous system and then spread to the central dopaminergic neurons through the gut–brain axis, suggesting the contribution of an altered gut microenvironment in the pathogenesis of PD. A plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with PD compared to unaffected controls. Chronic gut inflammation and impaired intestinal barrier integrity have been observed in human PD patients and mouse models of PD. These observations led to the hypothesis that an altered gut microenvironment is a potential trigger of the PD process in a genetically susceptible host. In this review, we will discuss the complex interplay between genetic factors and gut microenvironmental changes contributing to PD pathogenesis.

show abstract

Section: Metagenomic and Metabolomic Evidence Of Gastrointestinal Inv...mentioning

confidence: 99%

Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis

Chen

Lin

2022

J Biomed Sci

View full text Add to dashboard Cite

show abstract

“…Therefore, understanding how the secreted bacterial elements can interfere with protein homeostasis in EECs is a new path of investigation to understand the contribution of these cells to PD pathology. This protocol describes the detailed obtention of the conditioned-medium (CM) from the anaerobic microorganism A. muciniphila which is known to modulate intracellular calcium (Ca 2+ ) signaling in EECs and induce αSyn pathology in the same cell model ( Amorim Neto et al., 2022 ). In addition, we explain here how this CM can be used to monitor Ca 2+ signaling in EECs under confocal live imaging.…”

Section: Before You Beginmentioning

confidence: 99%

“…This protocol was written with a focus on Akkermansia muciniphila CM. Originally the Escherichia coli CM was also fractionated and also concentrated into >3 kDa and <3 kDa fractions and used to stimulate STC-1 cells in different experimental approaches ( Amorim Neto et al., 2022 ). However, NMR analysis of the concentrated fractions was done only for BHI CM from Akkermansia muciniphila .…”

Section: Limitationsmentioning

confidence: 99%

See 2 more Smart Citations

Protocol for rapid obtention and fractionation of anaerobic bacterial conditioned media to study calcium signaling in enteroendocrine cells

Neto¹,

Fonseca²

2022

STAR Protocols

Self Cite

View full text Add to dashboard Cite

Dysbiosis and Alzheimer’s disease: role of probiotics, prebiotics and synbiotics

Thakkar

Vora

Kaur

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

View full text Add to dashboard Cite

Akkermansia muciniphila induces mitochondrial calcium overload and α -synuclein aggregation in an enteroendocrine cell line

Cited by 40 publications

References 117 publications

Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis

Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis

Protocol for rapid obtention and fractionation of anaerobic bacterial conditioned media to study calcium signaling in enteroendocrine cells

Dysbiosis and Alzheimer’s disease: role of probiotics, prebiotics and synbiotics

Contact Info

Product

Resources

About