Lewy bodies appear as spherical masses in the
cytoplasm that displace other cell components. For instance, some Lewy bodies tend to displace the nucleus to one side of the cell.[better source needed][2] There are two main kinds of Lewy bodies: classical and cortical. Lewy bodies may be found in the
midbrain (within the
substantia nigra) or within the
cortex. A classical Lewy body is an
eosinophilic cytoplasmic inclusion consisting of a dense core surrounded by a halo of 10 nm wide radiating
fibrils, the primary structural component of which is
alpha-synuclein.
History
In 1910,
Fritz Heinrich Lewy was studying in
Berlin for his doctorate.[3] He was the first doctor to notice some unusual proteins in the brain, comparing them to earlier findings by
Gonzalo Rodríguez Lafora.[4] In 1913, Lafora described another case, and acknowledged Lewy as the discoverer, naming them cuerpos intracelulares de Lewy (intracellular Lewy bodies).[4]Konstantin Nikolaevich Trétiakoff found them in 1919 in the
substantia nigra of PD brains, called them corps de Lewy and is credited with the eponym.[4] In 1923, Lewy published his findings in a book, The Study on Muscle Tone and Movement. Including Systematic Investigations on the Clinic, Physiology, Pathology, and Pathogenesis of Paralysis agitans.[5] Eliasz Engelhardt, who is in the neurology department at
Federal University of Rio de Janeiro, argued in 2017 that Lafora should be credited with the eponym, because he named them six years before Trétiakoff.[4] Nonetheless,
Trétiakoff is still the primary figure acknowledged for coining the term, "Lewy bodies".[4]
According to the Journal of the History of the Neurosciences, Dr. Lewy became interested in studying more about the brain (
neurology), because of the discovery that
Alois Alzheimer made in 1906. The article mentions that the third reported case of
Alzheimer's disease had histological structures that happened to be similar to Lewy body histology slides, but the contribution was not given to Lewy's finding.[6]
Alpha-synuclein modulates
DNA repair processes, including repair of DNA
double-strand breaks (DSBs) by the process of
non-homologous end joining[12] The repair function of alpha-synuclein appears to be greatly reduced in Lewy body bearing
neurons, and this reduction may trigger cell death. Mutations are the reason behind their damaged repair function.[13] One mutation in particular, in the gene encoding for presynaptic alpha-synuclein, was found to have been passed down from family members with PD.[13] Similarly in regards to DLB, Lewy bodies retrieved from DLB brains were found to contain alpha-synuclein proteins that were shortened by mutations.[13]
Lewy bodies are believed to represent an
aggresome response in the cell.[14] When misfolded proteins aggregate, or clump together, many diseases are more likely to develop, including those that are associated with Lewy bodies.[15] Aggregation is believed to occur when there is a high amount of misfolded proteins in the ubiquitin-proteasome pathway, which are then brought to a resulting aggresome so they can be organized into one place.[15] Since Lewy bodies are made of ubiquitinated proteins that would be handled in the ubiquitin-proteasome pathway, they may be made from this or a similar process if the pathway capacity is indeed exceeded by misfolded proteins that aggregate together.[15] Accordingly, the aggresome, where the damaged proteins fully aggregate, is akin to the Lewy body.
Despite their differences, there is evidence that a particular protein family, called 14-3-3, plays a role in the formation of both cortical and classical Lewy bodies.[better source needed][16] This makes it an important protein family in regards to Lewy body-associated diseases, and there are at least 7 forms of it that have been clearly identified in mammals.[16]
Cortical Lewy bodies are also composed of alpha-synuclein fibrils, but are less defined and lack halos. This kind of Lewy body is one of those aforementioned that regularly displaces the nucleus.[2] In
histopathology, cortical Lewy bodies are a distinguishing feature for dementia with Lewy bodies, but may occasionally be seen in ballooned neurons characteristic of
behavioural variant frontotemporal dementia and
corticobasal degeneration,[17] as well as in patients with other
tauopathies.[18]
Lewy neurites
Lewy neurites are abnormal
neurites in diseased neurons, containing granular material and abnormal
α-synuclein filaments similar to those found in Lewy bodies.[19] Like Lewy bodies, Lewy neurites are a feature of
α-synucleinopathies such as dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy.[20] They are also found in the CA2-3 region of the
hippocampus in
Alzheimer's disease.[20]
^Jellinger KA (September 2007). "More frequent Lewy bodies but less frequent Alzheimer-type lesions in multiple system atrophy as compared to age-matched control brains". Acta Neuropathologica. 114 (3): 299–303.
doi:
10.1007/s00401-007-0227-4.
PMID17476513.
S2CID32406286.
^García-Albea E, Pérez Trullen JM (December 2003). "The Spanish school of neurology and the first American cases of Alzheimer's disease". Journal of the History of the Neurosciences. 12 (4): 437–45.
doi:
10.1076/jhin.12.4.437.27919.
PMID15069873.
S2CID40698888.
^Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (March–April 2003). "Staging of brain pathology related to sporadic Parkinson's disease". Neurobiology of Aging. 24 (2): 197–211.
doi:
10.1016/S0197-4580(02)00065-9.
PMID12498954.
S2CID22798538.
^Arima K, Hirai S, Sunohara N, Aoto K, Izumiyama Y, Uéda K, Ikeda K, Kawai M (October 1999). "Cellular co-localization of phosphorylated tau- and NACP/alpha-synuclein-epitopes in lewy bodies in sporadic Parkinson's disease and in dementia with Lewy bodies". Brain Research. 843 (1–2): 53–61.
doi:
10.1016/S0006-8993(99)01848-X.
PMID10528110.
S2CID11144367.
^Schmidt ML, Martin JA, Lee VM, Trojanowski JQ (1996). "Convergence of Lewy bodies and neurofibrillary tangles in amygdala neurons of Alzheimer's disease and Lewy body disorders". Acta Neuropathologica. 91 (5): 475–81.
doi:
10.1007/s004010050454.
PMID8740227.
S2CID19770377.
^Dickson DW, Feany MB, Yen SH, Mattiace LA, Davies P (1996). "Cytoskeletal pathology in non-Alzheimer degenerative dementia: New lesions in Diffuse Lewy body disease, Pick's disease, and Corticobasal Degeneration". New Trends in the Diagnosis and Therapy of Non-Alzheimer's Dementia. Journal of Neural Transmission Supplement. Vol. 47. pp. 31–46.
doi:
10.1007/978-3-7091-6892-9_2.
ISBN978-3211828236.
PMID8841955. {{
cite book}}: |journal= ignored (
help)
^
abMarui W, Iseki E, Kato M, Akatsu H, Kosaka K (August 2004). "Pathological entity of dementia with Lewy bodies and its differentiation from Alzheimer's disease". Acta Neuropathologica. 108 (2): 121–128.
doi:
10.1007/s00401-004-0869-4.
PMID15235805.
S2CID22624886.
External links
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