IL ‐1β/IL‐1R1 signaling is involved in the propagation of α‐synuclein pathology of the gastrointestinal tract to the brain

Graphical abstract demonstrating IL-1 β/IL-1R1-dependent α-syn aggregation in the enteric nervous system and its propagation to brain. (1) The rotenone interacts with colon endothelial cells and (2) induces the activation of immune-inflammatory cells, including macrophages, release cytokines such as IL-1β. (3) IL-1 β binds to IL-1R1 on the surface of the ENS (Enteric nervous system) and (4) induces the accumulation of the α-syn, which further propagates to the DMV via the vagus nerve. (5) The aggregated α-syn from gastrointestinal tract into the DMV and to other brain parts as follows: ICP (inferior cerebellar peduncle), AM B (ambiguous nucleus), N7 (cranial nerve seven), ROB (raphe obscurus nucleus), PAG (periaqueductal gray), P.R. (prerubral field), LM/ML (lateral and medial mammillary nucleus), AHiPM (amygdalohippocampal area, posteromedial part), AVP (anteroventral periventricular nucleus), BSTMV (bed nucleus of st ria terminalis, ventral part), BSTLP (bed nucleus of stria terminalis, lateral part), and Pir (piriform cortex). AbstractThe pathological hallmark of Parkinson's disease (PD) is the intraneuronal accumulation of misfolded alpha-synuclein (termed Lewy bodies) in dopaminergic neurons of substantia nigra par compacta (SNc). It is assumed that the α-syn pathology is induced by gastrointestinal inflammation and then transfers to the brain by the gut-brain axis. Therefore, the relationship between gastrointestinal inflammation and α-syn pathology leading to ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research