HomeENGLISH MAGAZINEToo much abnormal protein makes the neurons Syk: once in a while...

Too much abnormal protein makes the neurons Syk: once in a while a kinase turns from perpetrator into a patron

Unfortunately, medicine currently lacks effective treatments to target the root causes of most neurodegenerative diseases, such as Alzheimer’s, Parkinson’s or ALS. UVA Health researchers have discovered a cellular protein in the brain orchestrates the immune system’s responses to Alzheimer’s and multiple sclerosis (MS), potentially enabling doctors to enhance the body’s ability to fight those and other serious neurological diseases. The molecule the researchers identified, called the protein tyrosine kinase SYK, is critical both for removing the plaque buildup associated with Alzheimer’s and preventing the buildup of debris that causes MS, the researchers found. And it would do so by directing the activity of the brain’s scavenger cells called microglia. These immune cells were once largely ignored by scientists but, in recent years, have proved vital players in brain health.

Many neurodegenerative diseases, including Alzheimer’s, ALS and MS, are thought to be caused by the brain’s inability to break free from the buildup of toxic proteins. The abundant presence of microglia in the lesions would be proof of this. Recent advances in neuroscience research have shed light on the importance of microglia in removing harmful debris from the brain, but the new discovery offers practical insights into how this cleansing process occurs and the disastrous consequences if it does not. These latest findings may one day allow doctors to increase microglia activity to treat or protect patients from Alzheimer’s, MS and other neurodegenerative diseases. Using a mouse model of Alzheimer’s disease, the UVA researchers found that the lack of the spleen tyrosine kinase, or Syk, triggered the buildup of plaques in the brain and caused the mice to lose memory, such as symptoms. observed in humans with Alzheimer’s disease.

Additionally, neuroscientists have been able to reduce plaque buildup by activating this molecule and microglia in the brain, suggesting a potential therapeutic approach for human patients, even though this would require far more research and testing. The process is made more difficult by the fact that there are only experimental inhibitors of the Syk protein, studied as immunosuppressants, but not its direct activators. Syk kinase, in fact, needs to be activated through cell receptors, through molecular passages. The lack of the molecule in a mouse model of MS, meanwhile, led to the accumulation of damaged myelin, a protective coating on nerve cells. When myelin is damaged, cells cannot properly transmit messages, causing MS symptoms such as mobility problems and muscle spasms. In an additional publication, the UVA researchers concluded that the SYK protein kinase is “critically involved” in the crucial removal of myelin debris.

John Lukens, PhD, senior research fellow at the Carter Immunology Center and UVA Brain Institute, explained in depth: “In our studies, we discovered a central regulator of the cell type and processes needed to protect the brain from these disorders. Our work also shows that targeting this new path provides a powerful strategy for eliminating the toxic culprits that cause memory loss and poor motor control in neurodegenerative diseases. While increasing SYK activity in microglia can reduce the amount of myelin debris in MS lesions, developing new drugs to target SYK could stop MS progression and help reverse the damage. This is a particularly promising option as most drugs currently available dampen adaptive immunity. This leads to susceptibility to infections and an increased risk of potentially fatal side effects, such as progressive multifocal leukoencephalopathy. In addition, some forms of MS do not have strong immune involvement and therefore there are currently very limited treatment options for that type of patients”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Ennerfelt H, Frost EL et al. Cell 2022 Oct 6 in press.

Ennerfelt H, Lukens JR. Immunol Rev. 2020; 297(1):225.

Yong HYF, Yong VW. Nat Rev Neurol. 2022; 18(1):40-55. 

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Dott. Gianfrancesco Cormaci

Medico Chirurgo, Specialista; PhD. a CoFood s.r.l.
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento enzimaticamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (Leader of the R&D for the partnership CoFood s.r.l.) - Autore di articoli su informazione medica e salute sul sito www.medicomunicare.it (Medical/health information on website) - Autore di corsi ECM FAD pubblicizzati sul sito www.salutesicilia.it
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