alpha-Synuclein: a Modulator During Inflammatory CNS Demyelination.
Kristina KuhbandnerAlana HoffmannMaría Nazareth González AlvaradoLisa SeylerTobias BäuerleJuergen WinklerRalf A LinkerPublished in: Journal of molecular neuroscience : MN (2020)
Neuroinflammation and demyelination are hallmarks of several neurological disorders such as multiple sclerosis and multiple system atrophy. To better understand the underlying mechanisms of de- and regeneration in respective diseases, it is critical to identify factors modulating these processes. One candidate factor is alpha-Synuclein (aSyn), which is known to be involved in the pathology of various neurodegenerative diseases. Recently, we have shown that aSyn is involved in the modulation of peripheral immune responses during acute neuroinflammatory processes. In the present study, the effect of aSyn deficiency on de- and regenerative events in the CNS was analyzed by using two different demyelinating animal models: chronic MOG35-55-induced experimental autoimmune encephalomyelitis (EAE) and the cuprizone model. Histopathological analysis of spinal cord cross sections 8 weeks after EAE induction revealed a significant reduction of CNS inflammation accompanied by decreased myelin loss during late-stage inflammatory demyelination in aSyn-deficient mice. In contrast, after cuprizone-induced demyelination or remyelination following withdrawal of cuprizone, myelination and neuroinflammatory patterns were not affected by aSyn deficiency. These data provide further evidence for aSyn as regulator of peripheral immune responses under neuroinflammatory conditions, thereby also modulating degenerative events in late-stage demyelinating disease.
Keyphrases
- immune response
- oxidative stress
- multiple sclerosis
- drug induced
- stem cells
- diabetic rats
- spinal cord
- blood brain barrier
- high glucose
- signaling pathway
- magnetic resonance
- white matter
- traumatic brain injury
- liver failure
- dendritic cells
- toll like receptor
- spinal cord injury
- magnetic resonance imaging
- electronic health record
- single cell
- replacement therapy
- hepatitis b virus
- inflammatory response
- cell therapy
- machine learning
- lps induced
- respiratory failure
- neuropathic pain
- smoking cessation
- gestational age
- aortic dissection
- wound healing