The Growing Recognition of Inflammation in Parkinson’s Disease

Apr, 2024

For over two centuries since James Parkinson first documented the motor impairments of his namesake disorder, researchers have endeavored to better comprehend what triggers Parkinson’s disease (PD) and how to more effectively moderate its symptoms. While damage to brain cells that produce the neurotransmitter dopamine was long considered central to the condition, scientists have developed a deeper insight into the intertwined interplay between heredity, environment, and the immune system that propels the pathogenesis of PD. Compelling evidence summarized in a recent review published in Nature Reviews Immunology points to inflammation playing a critical—and potentially earlier than anticipated—job in the degenerative process.

PD has traditionally been characterized as a motor dysfunction typified by tremors, rigidity, and slowed motions. However, it is now understood as a multi-system disorder impacting areas like slumber, cognition, and the gut, sometimes many years before motor signs emerge. The review underscores several investigations detecting markers of intestinal inflammation and immune abnormalities in PD patients, correlating with earlier disease outset. This lends backing to the concept that triggers like intestinal bacteria or viral infections initially provoke peripheral inflammation that ultimately spreads inward to the brain.

Regarding heredity, over twenty genes have been implicated in familial types of PD, many coding for proteins occupied in operations like lysosomal work and mitophagy—the selective breakdown of damaged mitochondria. Numerous such genes, involving LRRK2 and GBA, are strongly communicated in immune cells and fine-tune their responses. Variants in these and other genes connected to immune signaling have additionally been related to augmented sporadic PD risk. Moreover, modifications in inflammatory cytokines like TNF are more prevalent in PD patients and worsen condition progression.

Inside the brain, microglia—the resident immune cells—adopt an activated phenotype in PD-impacted regions. Studies in humans and animal models point to pro-inflammatory signaling from microglia and infiltrating T cells in neurotoxicity. Peripheral immune profiles further reflect dysregulation, with shifts in monocyte, B and T cell populations observed. Many findings indicate to HLA genes overseeing antigen presentation as probable links between heredity and environment.

Remarkably, epidemiological data tie PD hazard to a family of autoimmune disorders, with up to a 30% increased likelihood among patients. Treatment with anti-TNF biologics to curb intestinal inflammation, in turn, may diminish PD incidence by almost 80%. Such correlations provide population-level confirmation of inflammation’s character.

Taken together, this confirmation argues inflammation should no longer be viewed as simply a secondary consequence or comorbidity of PD, but an early impetus actively shaping disease risk and progression. It offers hope that future treatments targeting neuroinflammation, particularly in pre-symptomatic stages, may retard or even stave off neurodegeneration—representing a promising new therapeutic frontier in the battle against Parkinson’s disease.




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About the Author

  • Dilruwan Herath

    Dilruwan Herath is a British infectious disease physician and pharmaceutical medical executive with over 25 years of experience. As a doctor, he specialized in infectious diseases and immunology, developing a resolute focus on public health impact. Throughout his career, Dr. Herath has held several senior medical leadership roles in large global pharmaceutical companies, leading transformative clinical changes and ensuring access to innovative medicines. Currently, he serves as an expert member for the Faculty of Pharmaceutical Medicine on it Infectious Disease Commitee and continues advising life sciences companies. When not practicing medicine, Dr. Herath enjoys painting landscapes, motorsports, computer programming, and spending time with his young family. He maintains an avid interest in science and technology. He is a founder of DarkDrug

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