Abstract
Humans evolved a symbiotic relationship with their gut microbiome, a complex microbial community composed of bacteria, archaea, protists, and viruses, including bacteriophages. The enteric nervous system (ENS) is a gateway for the bidirectional communication between the brain and the gut, mostly through the vagus nerve (VN). Environmental exposure plays a pivotal role in both the composition and functionality of the gut microbiome and may contribute to susceptibility to neurodegenerative disorders, such as Parkinson's disease (PD). The neuropathological hallmark of PD is the widespread appearance of alpha-synuclein aggregates in both the central and peripheral nervous systems, including the ENS. Many studies suggest that gut toxins can induce the formation of α-syn aggregates in the ENS, which may then be transmitted in a prion-like manner to the CNS through the VN. PD is strongly associated with aging and its negative effects on homeostatic mechanisms protecting from inflammation, oxidative stress, and protein malfunction. In this mini-review, we revisit some landmark discoveries in the field of Parkinson's research and focus on the gut-brain axis. In the process, we highlight evidence showing gut-associated dysbiosis and related microbial-derived components as important players and risk factors for PD. Therefore, the gut microbiome emerges as a potential target for protective measures aiming to prevent PD onset.
Highlights
Parkinson’s Disease (PD) is a common neurodegenerative disorder typically associated with the progressive loss of dopaminergic neurons located in the midbrain nucleus substantia nigra pars compacta (SNpc) [1]
Aggregates of α-syn fibrils are found in neural tissue located outside the central nervous system (CNS) of Parkinson’s disease (PD) patients, in both the autonomic and enteric nervous system (ENS), an outcome which may be associated with the non-motor symptoms of the disease [for review, see [3]]
Aging is the main risk factor for the development of PD [140] and delaying the aging process is neuroprotective to PD in animal models [141]
Summary
Parkinson’s Disease (PD) is a common neurodegenerative disorder typically associated with the progressive loss of dopaminergic neurons located in the midbrain nucleus substantia nigra pars compacta (SNpc) [1]. The study may serve as the basis for a better understanding of molecular mechanisms involved in α-syn fibril nucleation and propagation Such structural information may provide useful insights on possible interactions of α-synuclein with other proteins and small molecules and allow the emergence of new tools with potential to facilitate both the diagnosis and treatment of PD (e.g., imaging agents and therapeutic drugs). Aggregates of α-syn fibrils are found in neural tissue located outside the central nervous system (CNS) of PD patients, in both the autonomic and enteric nervous system (ENS), an outcome which may be associated with the non-motor symptoms of the disease [for review, see [3]]. As other intestinal epithelial cells, enteroendocrine cells express toll-like receptors [86], allowing them to detect bacterial products, and activate vagal afferents through basal processes called neuropods (see Figure 1) [20, 87]
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