α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Chandra, Rashmi; Hiniker, Annie; Kuo, Yien–Ming; Nussbaum, Robert L.; Liddle, Rodger A.

doi:10.1172/jci.insight.92295

Cited by 187 publications

(213 citation statements)

References 68 publications

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“…Recent data show that synucleinopathies actually begin in the periphery and then spread into the central nervous system. Pathogenic alpha-synuclein appears to travel along vagus nerve afferents [140–142], which terminate in the nucleus of the solitary tract and dorsal motor nucleus of the vagus, which sits in close apposition to REM sleep circuitry (i.e., the SLD and vM). Therefore, synucleinopathies may initially impact the cells that control REM sleep atonia before spreading rostrally into the brain structures (e.g., substantia nigra and cortex) that cause the classic cognitive and motor impairments associated with synucleinopathies.…”

Section: Pathobiology Of Rem Sleepmentioning

confidence: 99%

Neuroscience: A Distributed Neural Network Controls REM Sleep

Peever

Fuller

2016

Current Biology

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Considerable advances in our understanding of the mechanisms and functions of rapid-eye-movement (REM) sleep have occurred over the past decade. Much of this progress can be attributed to the development of new neuroscience tools that have enabled high-precision interrogation of brain circuitry linked with REM sleep control, in turn revealing how REM sleep mechanisms themselves impact processes such as sensorimotor function. This review is intended to update the general scientific community about the recent mechanistic, functional and conceptual developments in our current understanding of REM sleep biology and pathobiology. Specifically, this review outlines the historical origins of the discovery of REM sleep, the diversity of REM sleep expression across and within species, the potential functions of REM sleep (e.g., memory consolidation), the neural circuits that control REM sleep, and how dysfunction of REM sleep mechanisms underlie debilitating sleep disorders such as REM sleep behaviour disorder and narcolepsy.

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Section: Pathobiology Of Rem Sleepmentioning

confidence: 99%

Neuroscience: A Distributed Neural Network Controls REM Sleep

Peever

Fuller

2016

Current Biology

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“…( F ) Immunofluorescence demonstrating α‐synuclein–positive cells (green) in the gut mucosa, in close association with enteric nerves (red), and demonstrating colocalisation of α‐synuclein in the enteric nerves (yellow), with permission from Chandra et al . , though the presence of α‐synuclein in the gut is not completely specific for synucleinopathy, as it is also seen in controls. Together these images illustrate how both nose and gut access points are implicated in neuropathology in PD, AD and MS.…”

Section: Nasal Cavitymentioning

confidence: 90%

“…Constipation occurs in 60–80% of PD patients and is often one of the earliest symptoms , occurring up to 20 years before clinical onset . Remarkably, α‐synuclein deposits are observed in the enteric nervous system from the earliest disease stages (Figure F ), often before the onset of motor pathology . Together, these findings have led to the suspicion that PD pathology may initiate in the gut, before spreading to the brain.…”

Section: Gutmentioning

confidence: 99%

Invited Review: From nose to gut – the role of the microbiome in neurological disease

Bell

Spencer

Yates

et al. 2018

Neuropathology Appl Neurobio

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Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system (CNS) in health and disease. To date, most research has focussed on a gut‐brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces – the nose, mouth, lung and gut – in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or CNS‐specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease.

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“…The accumulation of infections throughout life combined with increased expression of α-synuclein during the aging process may increase susceptibility to PD (Bu et al, 2015). Both mouse and human enteroendocrine cells, which border the gut lumen and synapse with enteric nerves, express α-synuclein (Chandra et al, 2017). This provides an intriguing potential direct link between events within the gut, such as microbial dysbiosis, and changes in α-synuclein expression and higher order structure.…”

Section: Mechanisms: Inflammationmentioning

confidence: 99%

Bottoms up: the role of gut microbiota in brain health

Radisavljevic

Cirstea

2019

Environmental Microbiology

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Summary The gut microbiota affects many aspects of human health, and research, especially over the past decade, is demonstrating that the brain is no exception. This review summarizes existing human observational studies of the microbiota in brain health and neurological conditions at all ages, as well as animal studies that are advancing the field beyond correlation and into causality. Potential mechanisms by which the brain and the gut microbiota are connected are explored, including inflammation, bacterially‐produced metabolites and neurotransmitters and specific roles for individual microbes. Finally, important challenges and potential mitigation strategies are discussed, as well as ways in which some of these same challenges can be harnessed to advance our understanding of this complex, exciting and rapidly evolving field.

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α-Synuclein in gut endocrine cells and its implications for Parkinson’s disease

Cited by 187 publications

References 68 publications

Neuroscience: A Distributed Neural Network Controls REM Sleep

Neuroscience: A Distributed Neural Network Controls REM Sleep

Invited Review: From nose to gut – the role of the microbiome in neurological disease

Bottoms up: the role of gut microbiota in brain health

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