Gangliosides and Neurological Development

By Melissa Larcher

Recent developments in neuroscience have led to the discovery that glycolipid structures promote platelet activation and neuroinflammation, therefore having an imperative role neurological diseases such as Alzheimer’s Disease. Due to these recent developments new studies have shown that important developmental structures within the brain can also be a vital contributor towards finding preventative cures towards degenerative neural diseases.

Although it is known that platelets are one of the first responders when it comes to blood vessel damage, studies have shown they can also bind to sialated gangliosides integrated into lipid rafts in the brain (Sotnikov 2013). Sialated gangliosides are the molecules on the surface of nervous system cell membranes within lipid rafts that are pivotal for normal cell-to-cell communication (Molander-Melin 2005). Researchers found that platelets recognize the sialated gangliosides in lipid rafts that are on the surface of astroglial and neuronal cells (Sotnikov 2013). Specifically, platelets are going to recognize ligands CD62P, a type 1 transmembrane glycoprotein, a binding molecule that is found inside lipid rafts, astrocytes, and neurons which lead to platelet activation and degranulation. Slotnikov et al’s study follows the development of a model of neuroinflammatory and neurodegenerative diseases such as Alzheimer’s Disease and Multiple Sclerosis which has led to the understanding of new types of neuronal damage signals that involve platelets as the main signal transducers . It has been implicated that factors affecting the expression of the specific ganglioside, GM1, may be the precursor to neuronal problems such as Alzheimer’s Disease (Zlokovic 2011).

Pertaining to Alzheimer’s Disease, a progressive disease that leads to memory deficits and other important mental functions, the lipid raft associated ganglioside GM1 expression may affect the onset of neuronal problems. GM1 down expression is an early onset precursor of Alzheimer’s Disease. Without proper GM1 expression platelets cannot recognize the lipid rafts which require neuroinflammation, thus, leading to an early onset of Alzheimer’s Disease and other such related neuronal diseases such as MS (Schengrund 2015). It has been known for some time that gangliosides, especially the ganglioside GM1, is also connected to Parkinson’s Disease. Damage to GM1 expression can lead to the inability to aggregate and form insoluble fibrils which are necessary for normal neuronal functions (Schengrund 2015). Appropriate interaction between GM1 and alpha-synuclein is essential for proper neurological function and amyloid-β transport in brain ( Zlokovic 2011). Schengrund’s research goes more into depth by referencing research in which a mutation of the ganglioside domain of alpha-synuclein causes it to be less conductive and eventually leads to a Parkinson’s-like disease in mice (Schengrund 2015).

These research studies indicate that expression of gangliosides within lipid rafts are essential for signal transduction and proper neurological development. Since several proteins are in correlation with numerous types of neurological diseases, it is possible that fixing gangliosides within lipids rafts could lead to the possible repair or preventative care to help patients with neurological disorders.

There is new coming evidence that changes the ganglioside composition associated with normal aging and is highly associated with people who have Alzheimer’s Disease, Parkinson’s Disease, and other neurological diseases. Researchers Schengrund and Sotnikov also reference other confounding factors that contribute to these neurodegenerative diseases, but gangliosides seem to be the main factor in all of the contributing studies. Overall, further research should be done pertaining to gangliosides and their affect on neurodegenerative diseases.


References

1. Molander-Melin, M., Blennow, K., Bogdanovic, N., Dellheden, B., Månsson, J.-E. and Fredman, P. (2005), Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent-resistant membrane domains. Journal of Neurochemistry, 92: 171–182. doi: 10.1111/j.1471-4159.2004.02849.x

2. Schengrund, Cara-Lynne. “Result Filters.” National Center for Biotechnology Information. U.S. National Library of Medicine, July 2015. Web. 24 May 2016.

3. Sotnikov I, Veremeyko T, Starossom SC, Barteneva N, Weiner HL, et al. (2013) Platelets Recognize Brain-Specific Glycolipid Structures, Respond to Neurovascular Damage and Promote Neuroinflammation. PLoS ONE 8(3): e58979. doi:10.1371/journal.pone.0058979

4. Zlokovic, Berislav V. “Neurovascular Pathways to Neurodegeneration in Alzheimer’s Disease and Other Disorders.” Nature reviews. Neuroscience 12.12 (2011): 723–738. PMC. Web. 16 June 2016..