Diya Adhikary, Amity University Kolkata
Fritz Jacob Heinrich Lewy (German neurologist) was the first to identify eosinophilic inclusion bodies in neurons of certain brain nuclei. These “eosinophilic inclusion bodies” also referred to as Lewy bodies, were named after him. He described the pathology of Paralysis agitans (the term for, Parkinson’s disease).
LOCATION: Lewy bodies are located in the nigrostriatal neurons in the case of Parkinson’s disease. The substantia nigra, which is located in the midbrain portion of the brainstem, is mainly affected in this case. The areas beyond the brainstem, including the cortex (the thinking part) of the brain, can also be affected.
DESCRIPTION: In Parkinson’s disease (PD), a slowly progressing neurodegenerative disorder, the pathological hallmarks are the degeneration of nigrostriatal dopamine neurons and the presence of alpha-synuclein containing inclusions (Lewy bodies) in afflicted brain regions.
Lewy bodies are 140-amino-acid long proteinaceous structures having radiating filaments. These dense, circular, concentric ring-shaped structures of aggregated intra-cytoplasmic proteins, can migrate across cells of connected brain regions.
CAUSES: When the alpha-synuclein gets deposited in the brain, it prevents the brain from making the right amount of acetylcholine and dopamine. The deficiency of acetylcholine affects memory and learning abilities. Dopamine acts as a messenger between the substantia nigra and the corpus striatum to produce smooth and controlled movements. Hence, its deficiency leads to ineffective communication between the two brain areas, resulting in impaired movement, ultimately causing motor problems.
So far 5 genes (SNCA, PARK2, PARK7, PINK1, LRRK2) associated with the disease have been identified. Several other chromosomal regions and genes like GBA, SNCAIP, and UCHL1 may also be linked. Fewer than 10 % of cases are due to a single gene mutation, and not all people manifesting this particular mutation develop this disease. This hints at the fact that environmental factors are highly likely to have an impact that is significant enough to add to the development of the disease.
PATHWAY:
- Evidence from both toxin and genetic based models suggest a major etiologic role for mitochondrial dysfunction, protein aggregation, the ubiquitin-proteasome system and kinase signalling pathways in the pathogenesis of Parkinson’s disease.
- According to current evidence, the central cause of sporadic Parkinson’s disease might be mitochondrial complex-1 inhibition. Derangements in complex-1 cause alpha-synuclein aggregation, which further leads to the death of dopamine neurons. Accumulation and aggregation of alpha-synuclein through impairments in protein handling and detoxification, further contribute to the demise of dopamine neurons. Dysfunction of the ubiquitin E3 ligase, parkin and DJ-1 could also contribute to these deficits.
SYMPTOMS:
Primary Symptoms: Studies suggest that individuals with Parkinson’s disease will have lost 60% to 80% or more of the dopamine-producing cells in the brain. Characteristic motor symptoms include tremors, rigidity, bradykinesia, postural instability and Parkinsonian gait.
Secondary symptoms: May vary in severity, and not everyone with Parkinson’s will experience all of them, and may include anxiety, insecurity, stress, confusion, memory loss, dementia, constipation, depression, difficulty in swallowing, extensive salvation, diminished sense of smell, increased sweating, erectile dysfunction, skin problems, quieter speech, monotone voice and urinary frequency.
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REFERENCE:-
- Miklya, I., Pencz, N., Hafenscher, F., & Göltl, P. (2014). [The role of alpha-synuclein in Parkinson’s disease]. Neuropsychopharmacologia Hungarica: A Magyar Pszichofarmakologiai Egyesulet Lapja = Official Journal of the Hungarian Association of Psychopharmacology, 16(2), 77–84.https://pubmed.ncbi.nlm.nih.gov/24978050/
- https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055
- https://www.nia.nih.gov/health/parkinsons-disease
- https://www.medicinenet.com/parkinsons_disease/article.htm
- https://academic.oup.com/hmg/article/14/18/2749/2355831
- https://science.sciencemag.org/content/302/5646/819
- https://www.medicinenet.com/parkinsons_disease/article.htm#what_is_the_treatment_for_parkinsons_disease
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