PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 22, 2024

Abstract Parkinson’s disease (PD) is characterized by a protracted period of non-motor symptoms, including gastrointestinal (GI) dysfunction, which can precede the development cardinal motor deficits decades. This long prodrome highly suggestive immune cell involvement in initiation disease, but currently field lacks robust model systems to study such mechanisms. It has been hypothesized that pathology may be first initiated periphery due environmental triggers, as pathogens enter GI tract. We further speculate impact on system could exacerbated genetically predisposed individuals. Our group developed GI-targeted pathogen-induced PD mouse PINK1 KO mice with Gram-negative bacterial infections and found T cells are major player driving PD-like symptoms at late stages following infection. Herein, we now map initiating events site infection earliest goal shedding light mechanisms triggering immune-mediated pathological processes relevant PD. Using unbiased single sequencing, demonstrate myeloid dysregulated type infected 1-week post-infection, followed response shortly after, 2 weeks post-infection. find these have an enhanced proinflammatory profile, more mature, develop capacity for antigen presentation. prediction analysis, our data suggest cytotoxic particularly poised interacting each other, identify possible direct cell-cell interaction pathways might implicated. Taken together, deciphering underpinning autoimmunity will instrumental effective therapeutic targeting strategies before irrevocable neuronal damage ensues.

Language: Английский

PINK1 deficiency rewires early immune responses in a mouse model of Parkinson’s disease triggered by intestinal infection

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 27, 2024

Parkinson’s disease (PD) is characterized by a protracted period of non-motor symptoms, including gastrointestinal (GI) dysfunction, which can precede the development cardinal motor deficits decades. This long prodrome highly suggestive immune cell involvement in initiation disease, but currently field lacks robust model systems to study such mechanisms. It has been hypothesized that pathology may be first initiated periphery due environmental triggers, as pathogens enter GI tract. We further speculate impact on system could exacerbated genetically predisposed individuals. Our group developed GI-targeted pathogen-induced PD mouse PINK1 KO mice with Gram-negative bacterial infections and found T cells are major player driving PD-like symptoms at late stages following infection. Herein, we now map initiating events site infection earliest goal shedding light mechanisms triggering immune-mediated pathological processes relevant PD. Using unbiased single sequencing, demonstrate myeloid dysregulated type infected 1-week post-infection, followed response shortly after, 2 weeks post-infection. find these have an enhanced proinflammatory profile, more mature, develop capacity for antigen presentation. prediction analysis, our data suggest cytotoxic particularly poised interacting each other, identify possible direct cell-cell interaction pathways might implicated. Taken together, deciphering underpinning autoimmunity will instrumental effective therapeutic targeting strategies before irrevocable neuronal damage ensues.

Language: Английский

Effects of Probiotics on Neurodegenerative Disease-Related Symptoms and Systemic Inflammation: A Systematic Review

International Journal of General Medicine, Journal Year: 2024, Volume and Issue: Volume 17, P. 5941 - 5958

Published: Dec. 1, 2024

In recent years, probiotics, as a class of biologically active microorganisms, have increasingly attracted attention for their potential in treating neurodegenerative diseases (NDDs). To comprehensively assess the effects probiotics on clinical symptoms and systemic inflammation regulation various NDDs, this systematic review conducted detailed search Cochrane Library, Embase, PubMed, Web Science databases, ultimately including 22 eligible randomized controlled trials (RCTs), with 4 RCTs Alzheimer's Disease (AD), 10 Parkinson's (PD), 2 Multiple Sclerosis (MS), Mild Cognitive Impairment (MCI), intervention durations ranging from to 16 weeks. The comprehensive analysis indicates that help improve related gastrointestinal function, cognitive quality life, mental health. Additionally, generally positive effect reducing enhancing antioxidant capacity patients. conclusion, existing evidence supports promising NDDs. However, further large-scale, high-quality studies are needed explore specific differences efficacy among probiotic strains, dosages, modes administration. Moreover, considering lifestyle dietary habits may modulate these external factors should also be included research considerations gain more understanding mechanisms application strategies NDDs treatment.

Language: Английский