Toll-Like Receptors, Inflammatory Pathways, and Gut Microbiota in Parkinson's Disease: Unraveling th
- OLCIAS
- Jul 5, 2023
- 3 min read
Talk Title: Toll-Like Receptors, Inflammatory Pathways, and Gut Microbiota in Parkinson's Disease: Unraveling the Links to Neurodegenerative Disorders
Author: Dr Uday Sankar Akash Vankayala Kaloji Narayana Rao University of Health Sciences, India Dearborn cardiology, Michigan, US Email ID: usavankayala@gmail.com Volume: Parkinson's Disease 2023_CN37_AA03 The International Live Conference on Parkinson's Disease Date: July 15, 2023 Time: 8 PM Indian Standard Time Location: Online Conference Theme: The Future of Parkinson's Disease Research and Clinical Practice Abstract:
Description:
Parkinson’s disease (PD) is an incurable progressive neurodegenerative disease characterized by pathological protein aggregation(α-synuclein) and neurodegeneration which involves all the districts of brain especially substantia nigra.
Characteristic:
Age group seen: >65yrs
Tremors often termed as “pill rolling” - resting tremors
Rigidity commonly known as cog wheel rigidity
Akinesia or bradykinesia slowing of movements
Postural instability: Highlighting Features
Shuffling gait
Outline:
Parkinson’s not only affects the central, but also autonomic and enteric nervous system. Toll-like receptors (TLRs) are a family of pattern recognitions receptors that play a crucial role in innate immune receptors primarily located on microglia, other immune cells as well as enteric nervous system. They have shown to express pivotal roles in recognizing exogenous and endogenous stimuli and triggering inflammatory response.
Pathophysiology:
The TLRs are activated by the abnormal protein aggregates in the neurons and lead to neuronal damage. TLR2 and TLR4 are especially implicated in this process. They also shape and develop the enteric nervous system, that are in turn dysregulated in patients with PD, and may thus be central to chronic gut dysfunction in PD. Increased proinflammatory cytokine concentrations in the blood and cerebrospinal fluid (CSF), the presence of activated microglia in various brain regions, including the substantia nigra, the infiltration of peripheral inflammatory cells in affected brain regions, and altered cellular immunity, including defects in monocyte phagocytosis, are all indicators of neuroinflammation in PD patients. Hence, high level of expression is hypothesized to aid the clearance of alpha synuclein in an acute phase but chronically open a cascade of neurodegeneration and neuroinflammation. This ultimately leads to a positive feedback loop for chronic gut dysfunction, promoting α-synuclein aggregation in the brain, gut and vagus nerve.
Study Analysis:
Evidence has implicated the gut environment and the gut-brain axis in the pathogenesis and progression of PD. The microbiome significantly affects the highly bidirectional connection between the brain and the gut through integrated immunological, neuroendocrine, and neurological processes. Through a variety of biochemical and functional inputs, the gut microbiota and its pertinent metabolites interact with the host, altering the host's homeostasis and health. disturbances of gut homeostasis are thought to be a factor in the aggregation of alpha-synuclein in enteric neurons, which may eventually travel to the brain over decades and cause the typical central nervous system signs of PD, such as neurodegeneration and motor deficits.
Epitome of Abstract:
->Toll-like receptors (TLRs) are expressed excessively in PD brains that lead to dopaminergic neural loss. In this regard, TLR2, TLR4, and TLR9 have the most prominent roles.
->The gut microbiota significantly affects the pathogenesis of parkinsons thorugh intricate mechanisms.
->Therefore, therapy targeting TLRs with hope could serve as novel disease-modifying therapeutic targets in PD patients in the future.
Biography: Dr. Uday Sankar Akash Vankayala is a medical graduate from Mallareddy Institute of Medical Sciences with aspirations to pursue a career in the United States. Currently, he is undertaking a medical rotation at Dearborn Cardiology in Michigan. Driven by a fascination for the intricate mechanisms of the human body, he has worked diligently to become a compassionate and dedicated doctor, committed to delivering high-quality care to his patients. With a curious nature, he remains enthusiastic about learning and embracing new innovations and advancements in the field of medicine. Dr. Vankayala has actively engaged in research projects and case reports, alongside volunteering for numerous health camps, where he has consistently displayed empathy and a willingness to listen to those in need. He embraces challenges as opportunities for growth, fearlessly approaching problems and seeking assistance when required. Driven by a love for exploration, he enjoys traveling and immersing himself in new working environments. In his free time, he finds solace in reading, which allows him to unwind while gaining insights into diverse cultures and perspectives. Furthermore, Dr. Vankayala derives fulfillment from teaching and mentoring his colleagues and juniors, fostering a collaborative and supportive team environment. His ultimate goal is to contribute to a better future by ensuring accessible and exceptional healthcare for all, thereby nurturing a healthier society.
