Neuroimmunology: Difference between revisions

Neurodevelopmental disorders result from impairments of growth and development of the brain and nervous system and lead to many disorders. Examples of these disorders include [[Asperger syndrome]], [[traumatic brain injury]], [[communication]], speech and language disorders, genetic disorders such as [[fragile-X syndrome]], [[Down syndrome]], [[epilepsy]], and [[fetal alcohol syndrome]]. Studies have shown that [[autism spectrum disorders]] (ASDs) may present due to basic disorders of epigenetic regulation.<ref>{{cite journal | author1 = Herbert M.R.|author1-link=Martha Herbert|author2=Russo J.P.|author3=Yang S.|author4=Roohi J.|author5=Blaxill M.|author6=Kahler S.G.|author7=Cremer L.|author8=Hatchwell E. | year = 2006 | title = Autism and environmental genomics | journal = Neurotoxicology | volume = 27 | issue = 5| pages = 671–684 | doi=10.1016/j.neuro.2006.03.017|pmid=16644012|bibcode=2006NeuTx..27..671H }}</ref> Other neuroimmunological research has shown that deregulation of correlated epigenetic processes in ASDs can alter gene expression and brain function without causing classical genetic lesions which are more easily attributable to a cause and effect relationship.<ref>{{cite journal |author1=Badcock C. |author2=Crespi B. | year = 2006 | title = Imbalanced genomic imprinting in brain development: an evolutionary basis for the aetiology of autism | journal = Journal of Evolutionary Biology | volume = 19 | issue = 4| pages = 1007–1032 | doi=10.1111/j.1420-9101.2006.01091.x | pmid=16780503|s2cid=14628770 }}</ref> These findings are some of the numerous recent discoveries in previously unknown areas of gene misexpression.

Increasing evidence suggests that neurodegenerative diseases are mediated by erroneous epigenetic mechanisms. Neurodegenerative diseases include [[Huntington's disease]] and [[Alzheimer's disease]]. Neuroimmunological research into these diseases has yielded evidence including the absence of simple Mendelian inheritance patterns, global transcriptional dysregulation, multiple types of pathogenic [[RNA alterations]], and many more.<ref>{{cite journal |author1=Greene L.A. |author2=Liu D.X. |author3=Troy C.M. |author4=Biswas S.C. | year = 2007 | title = Cell cycle molecules define a pathway required for neuron death in development and disease |journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1772 | issue = 4| pages = 392–401 | doi=10.1016/j.bbadis.2006.12.003 | pmid=17229557 | pmc=1885990}}</ref> In one of the experiments, a treatment of Huntington’s disease with histone deacetylases (HDAC), an enzyme that removes acetyl groups from lysine, and DNA/RNA binding anthracylines that affect nucleosome positioning, showed positive effects on behavioral measures, neuroprotection, nuclesomenucleosome remodeling, and associated chromatin dynamics.<ref>{{cite journal |author1=Abel T. |author2=Zukin R.S. | year = 2008 | title = Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders | journal = Current Opinion in Pharmacology | volume = 8 | issue = 1| pages = 57–64 | doi=10.1016/j.coph.2007.12.002| pmc=2405764 | pmid=18206423}}</ref> Another new finding on neurodegenerative diseases involves the overexpression of HDAC6 suppresses the neurodegenerative phenotype associated with Alzheimer’s disease pathology in associated animal models.<ref>{{cite journal |author1=Pandey U.B. |author2=Nie Z. |author3=Batlevi Y. |author4=McCray B.A. |author5=Ritson G.P. |author6=Nedelsky N.B. |author7=Schwartz S.L. |author8=DiProspero N.A. |author9=Knight M.A. | year = 2007 | title = HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS | journal = Nature | volume = 447 | issue = 7146| pages = 859–863 | doi=10.1038/nature05853 | pmid=17568747|bibcode=2007Natur.447..860P |s2cid=4365061 |display-authors=etal}}</ref> Other findings show that additional mechanisms are responsible for the "underlying transcriptional and post-transcriptional dysregulation and complex chromatin abnormalities in Huntington's disease".<ref>{{cite journal |author1=Ballas N. |author2=Mandel G. | year = 2005 | title = The many faces of REST oversee epigenetic programming of neuronal genes | journal = Current Opinion in Neurobiology | volume = 15 | issue = 5| pages = 500–506 | doi=10.1016/j.conb.2005.08.015 | pmid=16150588|s2cid=32596790 }}</ref>

The nervous system and immune system require the appropriate degrees of cellular differentiation, organizational integrity, and neural network connectivity. These operational features of the brain and nervous system may make signaling difficult to duplicate in severely diseased scenarios. There are currently three classes of therapies that have been utilized in both animal models of disease and in human clinical trials. These three classes include DNA methylation inhibitors, HDAC inhibitors, and RNA-based approaches. DNA methylation inhibitors are used to activate previously silenced genes. HDACs are a class of enzymes that have a broad set of biochemical modifications and can affect DNA demethylation and synergy with other therapeutic agents. The final therapy includes using RNA-based approaches to enhance stability, specificity, and efficacy, especially in diseases that are caused by RNA alterations. Emerging concepts concerning the complexity and versatility of the epigenome may suggest ways to target genomewide cellular processes. Other studies suggest that eventual seminal regulator targets may be identified allowing with alterations to the massive epigenetic reprogramming during gametogenesis. Many future treatments may extend beyond being purely therapeutic and may be preventable perhaps in the form of a vaccine. Newer high throughput technologies when combined with advances in imaging modalities such as in vivo optical nanotechnologies may give rise to even greater knowledge of genomic architecture, nuclear organization, and the interplay between the immune and nervous systems.<ref>{{cite journal |author1=Rauch J. |author2=Knoch T.A. |author3=Solovei I. |author4=Teller K. |author5=Stein S. |author6=Buiting K. |author7=Horsthemke B. |author8=Langowski J. |author9=Cremer T. |author-link9=Thomas Cremer| year = 2008 | title = Light optical precision measurements of the active and inactive Prader–Willi syndrome imprinted regions in human cell nuclei | doi =10.1111/j.1432-0436.2007.00237.x | journal = Differentiation | volume = 76 | issue = 1| pages = 66–82 |pmid=18039333 |display-authors=etal}}</ref>

*{{cite book |author=Visser A, Goodkin K (eds) |title=Psychoneuroimmunology: stress, mental disorders, and health |publisher=American Psychiatric Press |location=Washington, DC |year=2000 |isbn=0-88048-171-4 }}<br/>technical.

*{{cite book |authoreditor=Ransohoff RM (ed) |title=Universes in delicate balance: chemokines and the nervous system |publisher=Elsevier |location=Amsterdam |year=2002 |isbn=0-444-51002-8 }}