Editing Myelin (section)

==Clinical significance==
===Demyelination===
{{Further|Demyelinating disease|Lesional demyelinations of the central nervous system}}
Demyelination is the loss of the myelin sheath insulating the nerves, and is the hallmark of some [[neurodegenerative]] [[autoimmune]] diseases, including [[multiple sclerosis]], [[acute disseminated encephalomyelitis]], [[neuromyelitis optica]], [[transverse myelitis]], [[chronic inflammatory demyelinating polyneuropathy]], [[Guillain–Barré syndrome]], [[central pontine myelinosis]], inherited demyelinating diseases such as [[leukodystrophy]], and [[Charcot–Marie–Tooth disease]].  People with [[pernicious anaemia]] can also develop nerve damage if the condition is not diagnosed quickly.  [[Subacute combined degeneration of spinal cord]] secondary to pernicious anaemia can lead to slight peripheral nerve damage to severe damage to the central nervous system, affecting speech, balance, and [[cognitive]] awareness. When myelin degrades, conduction of signals along the nerve can be impaired or lost, and the nerve eventually withers.{{Clarify|date=April 2014}} A more serious case of myelin deterioration is called [[Canavan disease]].

The [[immune system]] may play a role in demyelination associated with such diseases, including inflammation causing demyelination by overproduction of [[cytokine]]s via upregulation of [[Tumor necrosis factor-alpha|tumor necrosis factor]]<ref name="pmid9482240">{{cite journal|vauthors=Ledeen RW, Chakraborty G|title=Cytokines, signal transduction, and inflammatory demyelination: review and hypothesis|journal=Neurochemical Research|volume=23|issue=3|pages=277–89|date=March 1998|pmid=9482240|doi=10.1023/A:1022493013904 |s2cid=7499162}}</ref> or [[interferon]]. MRI evidence that docosahexaenoic acid [[Docosahexaenoic acid|DHA]] ethyl ester improves myelination in generalized peroxisomal disorders.<ref>{{cite journal |last1=Martinez |first1=Manuela |last2=Vazquez |first2=Elida |title=MRI evidence that docosahexaenoic acid ethyl ester improves myelination in generalized peroxisomal disorders |journal=Neurology |date=1 July 1998 |volume=51 |issue=1 |pages=26–32 |doi=10.1212/wnl.51.1.26 |pmid=9674774 |s2cid=21929640 |url=https://n.neurology.org/content/51/1/26}}</ref>

====Symptoms====
[[Demyelinating disease|Demyelination]] results in diverse symptoms determined by the functions of the affected neurons. It disrupts signals between the brain and other parts of the body; symptoms differ from patient to patient, and have different presentations upon clinical observation and in laboratory studies.

Typical symptoms include blurriness in the central visual field that affects only one eye, may be accompanied by pain upon eye movement, double vision, loss of vision/hearing, odd sensation in legs, arms, chest, or face, such as tingling or numbness ([[neuropathy]]), weakness of arms or legs, cognitive disruption, including speech impairment and memory loss, heat sensitivity (symptoms worsen or reappear upon exposure to heat, such as a hot shower), loss of dexterity, difficulty coordinating movement or balance disorder, difficulty controlling bowel movements or urination, fatigue, and tinnitus.<ref>Mayo Clinic 2007 and University of Leicester Clinical Studies, 2014{{full citation needed|date=July 2018}}</ref>

====Myelin repair====
{{Further|Remyelination}}
Research to repair damaged myelin sheaths is ongoing. Techniques include surgically implanting [[oligodendrocyte precursor cell]]s in the central nervous system and inducing [[Remyelination|myelin repair]] with certain [[antibodies]]. While results in mice have been encouraging (via [[stem cell]] transplantation), whether this technique can be effective in replacing myelin loss in humans is still unknown.<ref name="pmid14702638">{{cite journal|vauthors=Windrem MS, Nunes MC, Rashbaum WK, Schwartz TH, Goodman RA, McKhann G, Roy NS, Goldman SA|title=Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain|journal=Nature Medicine|volume=10|issue=1|pages=93–97|date=January 2004|pmid=14702638|doi=10.1038/nm974|s2cid=34822879}}
*{{cite web |date=January 20, 2004 |title=Stem Cell Therapy Replaces Missing Myelin In Mouse Brains |website=FuturePundit |url=http://www.futurepundit.com/archives/001901.html |access-date=March 22, 2007 |archive-date=June 14, 2011 |archive-url=https://web.archive.org/web/20110614173025/http://www.futurepundit.com/archives/001901.html |url-status=dead }}</ref> [[Parasympathomimetic drug|Cholinergic treatments]], such as [[acetylcholinesterase inhibitor]]s (AChEIs), may have beneficial effects on myelination, myelin repair, and myelin integrity. Increasing cholinergic stimulation also may act through subtle trophic effects on brain developmental processes and particularly on oligodendrocytes and the lifelong myelination process they support. Increasing [[oligodendrocyte]] cholinergic stimulation, [[Acetylcholinesterase inhibitor|AChEIs]], and other cholinergic treatments, such as [[nicotine]], possibly could promote myelination during development and myelin repair in older age.<ref name="pmid17070782">{{cite journal|vauthors=Bartzokis G|title=Acetylcholinesterase inhibitors may improve myelin integrity|journal=Biological Psychiatry|volume=62|issue=4|pages=294–301|date=August 2007|pmid=17070782|doi=10.1016/j.biopsych.2006.08.020 |s2cid=2130691}}</ref> [[GSK3B|Glycogen synthase kinase 3β]] inhibitors such as [[lithium chloride]] have been found to promote myelination in mice with damaged facial nerves.<ref name="pmid22355115">{{cite journal|vauthors=Makoukji J, Belle M, Meffre D, Stassart R, Grenier J, Shackleford G, Fledrich R, Fonte C, Branchu J, Goulard M, de Waele C, Charbonnier F, Sereda MW, Baulieu EE, Schumacher M, Bernard S, Massaad C|title=Lithium enhances remyelination of peripheral nerves|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=109|issue=10|pages=3973–78|date=March 2012|pmid=22355115|pmc=3309729|doi=10.1073/pnas.1121367109|bibcode=2012PNAS..109.3973M |doi-access=free}}</ref> Cholesterol is a necessary nutrient for the myelin sheath, along with [[vitamin B12]].<ref name="Petrov">{{cite journal|vauthors=Petrov AM, Kasimov MR, Zefirov AL|title=Brain Cholesterol Metabolism and Its Defects: Linkage to Neurodegenerative Diseases and Synaptic Dysfunction|journal=Acta Naturae|volume=8|issue=1|pages=58–73|date=2016|pmid=27099785|pmc=4837572 |doi=10.32607/20758251-2016-8-1-58-73}}</ref><ref name="Miller">{{cite journal|vauthors=Miller A, Korem M, Almog R, Galboiz Y|title=Vitamin B12, demyelination, remyelination and repair in multiple sclerosis|journal=Journal of the Neurological Sciences|volume=233|issue=1–2|pages=93–97|date=June 2005|pmid=15896807|doi=10.1016/j.jns.2005.03.009 |s2cid=6269094}}</ref>

===Dysmyelination===
'''Dysmyelination''' is characterized by a defective structure and function of myelin sheaths; unlike demyelination, it does not produce [[lesion]]s. Such defective sheaths often arise from genetic mutations affecting the biosynthesis and formation of myelin. The [[shiverer mouse]] represents one animal model of dysmyelination.  Human diseases where dysmyelination has been implicated include [[leukodystrophy|leukodystrophies]] ([[Pelizaeus–Merzbacher disease]], [[Canavan disease]], [[phenylketonuria]]) and [[schizophrenia]].<ref>{{cite journal|vauthors=Krämer-Albers EM, Gehrig-Burger K, Thiele C, Trotter J, Nave KA|title=Perturbed interactions of mutant proteolipid protein/DM20 with cholesterol and lipid rafts in oligodendroglia: implications for dysmyelination in spastic paraplegia|journal=The Journal of Neuroscience|volume=26|issue=45|pages=11743–52|date=November 2006|pmid=17093095|pmc=6674790|doi=10.1523/JNEUROSCI.3581-06.2006 }}</ref><ref>{{cite book|vauthors=Matalon R, Michals-Matalon K, Surendran S, Tyring SK|title=N-Acetylaspartate|chapter=Canavan disease: studies on the knockout mouse|series=Advances in Experimental Medicine and Biology|volume=576|pages=77–93; discussion 361–63|date=2006|pmid=16802706|doi=10.1007/0-387-30172-0_6|isbn=978-0-387-30171-6 }}</ref><ref>{{cite journal|vauthors=Tkachev D, Mimmack ML, Huffaker SJ, Ryan M, Bahn S|title=Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia|journal=The International Journal of Neuropsychopharmacology|volume=10|issue=4|pages=557–63|date=August 2007|pmid=17291371|doi=10.1017/S1461145706007334 |doi-access=free}}</ref>