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New Research Identifies Potential Pathway for Stopping Spread of Alpha-Synuclein

By October 27, 2021May 26th, 2022No Comments

New Research Identifies Potential Pathway for Stopping Spread of Alpha-Synuclein

A hallmark of Parkinson’s disease is the presence of Lewy bodies—abnormal clumps of protein primarily made of alpha-synuclein—the reduction of which is hypothesized to stop or slow the development and progression of Parkinson’s and related diseases such as dementia with Lewy bodies and multiple system atrophy. The mechanisms behind the formation of spread of alpha-synuclein are not well understood, but a paper published last month in Nature Communications sheds light on a signaling pathway that may prove to be a therapeutic target in these neurodegenerative diseases.

By stimulating the cells of mice to form alpha-synuclein, researchers observed an increased interaction between toll-like receptor 2 (TLR2) and the MyD88 gene, which increases the activity of a third player, nuclear factor kappa B (NF-κB). This signaling pathway activates the central nervous system’s inflammatory response and increases the production of alpha-synuclein. Importantly, researchers were able to decrease the activity of TLR2 by inhibiting its interaction with MyD88 via the nasal administration of peptides that correspond to wtTIDM (wild-type TLR2-interacting domain of MyD88) and wtNBD (wild-type NEMO-binding domain), and this decreased interaction reduced the spread of alpha-synuclein and protected dopaminergic neurons in the peptide-treated mice.

The results of the study suggest that the TLR2/MyD88/NF-κB pathway is important in the spread of alpha-synuclein and that wtTIDM and wtNBD may be useful in the treatment of Parkinson’s disease and other synucleinopathies.

Read the paper
CND Life Sciences

CND Life Sciences is the creator of the Syn-One Test™, the world’s first commercially available test to visualize abnormal, phosphorylated alpha-synuclein in cutaneous nerve fibers. The test is an objective, evidence-based diagnostic tool to aid in the diagnosis of Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, or REM sleep behavior disorder.