According to a new research published on March 9th, the protein alpha-synuclein plays a vital role in reducing neuronal homeostasis and triggering neurodegeneration.
Parkinsons disease is a neurodegenerative disorder, which can be described as clumping together, forming characteristic bodies. However, it has been difficult to determine whether alpha-synuclein aggregation can aid disease development or progression, and when the aggregates may act in the toxic disease cascade, or if they are instead harmless bystanders to a different malevolent process. This is especially because aggregation in cellular and animal models hasn''t been controlled in time or space
The authors decided to optobiology, a technique in which a protein of interest is fused to another protein that changes its conformation in response to light, allowing the behavior of the target protein to be selectively and reversibly altered. This method, for example, discovered when the wavelength of the appropriate wavelength fell on the mustard protein, triggering the aggregation of its alpha-synuclein partner.
The aggregates that formed were similar to those of Lewy bodies in many ways, including that they included several other key proteins like alpha-synuclein found in Lewy bodies in people with Parkinson''s disease. While the alpha-synuclein in the aggregates exhibited the same type of conformation as in many other diseases of misfolded proteins, the aggregates also induced disfolding in alpha-synuclein molecules that were previously known to do well,
Finally, the authors transmitted the genes for the alpha-synuclein-cryptochrome fusion protein to mice, directly into the substantia nigra, the neural structure in the brain that is most commonly affected by Parkinson''s disease, and surgically placed an optic fiber to provide light to the targeted cells. Light treatment sparked the formation of alpha-synuclein aggregates, neurodegeneration, and neurodegeneration, as well as Parkinson''s-like motor deficits.
Our findings demonstrate the potential for this optobiological system to reliably and controllably induce the formation of Lewy body-like aggregations in model systems, in order to better understand the dynamics and spread of Lewy body formation and spread, as well as their contribution to the pathogenesis of Parkinsons disease.
The question of Oueslati is: How do alpha-synuclein aggregates contribute to neuronal damage in Parkinsons disease? We have developed a new optogenetic-based experiment model that allows for the induction and real-time monitoring of alpha-synuclein clustering in vivo.
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