AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
View PDF
Submit Manuscript AI Chat Paper
Show Outline
Show full outline
Hide outline
Show full outline
Hide outline
Review Article | Open Access

Sleep-based therapy: A new treatment for amyotrophic lateral sclerosis

Qing Cai1Mengya Li1Qifang Li1,2( )
Department of Curative Anesthesia, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China
Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, China
Show Author Information


Amyotrophic lateral sclerosis (ALS) is a worldwide problem with no effective treatment. Patients usually die of respiratory failure. The basic pathological process of ALS is the degeneration and necrosis of motor neurons. Neuroglial cell dysfunction is considered closely related to the development of ALS. Sleep plays an important role in repairing the nervous system, and sleep disorders can worsen ALS. Herein, we review the pathogenesis of ALS and the neuroprotective mechanism of sleep-based therapy. Sleep-based therapy could be a potential strategy to treat ALS.


van Es MA, Hardiman O, Chio A, et al. Amyotrophic lateral sclerosis. Lancet 2017, 390(10107): 2084-2098.
Gruzman A, Wood WL, Alpert E, et al. Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis. PNAS 2007, 104(30): 12524-12529.
Barber SC, Shaw PJ. Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radic Biol Med 2010, 48(5): 629-641.
Taylor JP, Brown RH Jr, Cleveland DW. Decoding ALS: from genes to mechanism. Nature 2016, 539(7628): 197-206.
Canosa A, Grassano M, Barberis M, et al. A familial amyotrophic lateral sclerosis pedigree discordant for a novel p.Glu46Asp heterozygous OPTN variant and the p.Ala5Val heterozygous SOD1 missense mutation. J Clin Neurosci 2020, 75: 223-225.
Trias E, Kovacs M, King PH, et al. Schwann cells orchestrate peripheral nerve inflammation through the expression of CSF1, IL-34, and SCF in amyotrophic lateral sclerosis. Glia 2020, 68(6): 1165-1181.
Liu J, Wang F. Role of neuroinflammation in amyotrophic lateral sclerosis: cellular mechanisms and therapeutic implications. Front Immunol 2017, 8: 1005.
Gourie-Devi M, Panda S, Sharma A. Sleep disorders in amyotrophic lateral sclerosis: a questionnaire- based study from India. Neurol India 2018, 66(3): 700.
Bishir M, Bhat A, Essa MM, et al. Sleep deprivation and neurological disorders. Biomed Res Int 2020, 2020: 5764017
Eijk RPAV, Eijkemans MJC, Nikolakopoulos S, et al. Pharmacogenetic interactions in amyotrophic lateral sclerosis: a step closer to a cure? Pharmacogenomics J 2020, 20(2): 220-226.
Decker H, Piermartiri TCB, Nedel CB, et al. Guanosine and GMP increase the number of granular cerebellar neurons in culture: dependence on adenosine A2A and ionotropic glutamate receptors. Purinergic Signal 2019, 15(4): 439-450.
Ottestad-Hansen S, Hu QX, Follin-Arbelet VV, et al. The cystine-glutamate exchanger (xCT, Slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain. Glia 2018, 66(5): 951-970.
Foran E, Trotti D. Glutamate transporters and the excitotoxic path to motor neuron degeneration in amyotrophic lateral sclerosis. Antioxid Redox Signal 2009, 11(7): 1587-1602.
Zhong Z, Deane R, Ali Z, et al. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci 2008, 11(4): 420-422.
Winkler EA, Sengillo JD, Sagare AP, et al. Blood-spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice. PNS 2014, 111(11): E1035-E1042.
Gabel S, Koncina E, Dorban G, et al. Inflammation promotes a conversion of astrocytes into neural progenitor cells via NF-kappaB activation. Mol Neurobiol 2016, 53(8): 5041-5055.
Livne-Bar I, Wei J, Liu HH, et al. Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury. J Clin Invest 2017, 127(12): 4403-4414.
Hooten KG, Beers DR, Zhao W, et al. Protective and toxic neuroinflammation in amyotrophic lateral sclerosis. Neurotherapeutics 2015, 12(2): 364-375.
Jha MK, Jo M, Kim JH, et al. Microglia-astrocyte crosstalk: an intimate molecular conversation. Neuroscientist 2019, 25(3): 227-240.
Mashima K, Takahashi S, Minami K, et al. Neuroprotective role of astroglia in parkinson disease by reducing oxidative stress through dopamine- induced activation of pentose-phosphate pathway. ASN Neuro 2018, 10: 1759091418775562.
Dávila D, Fernández S, Torres-Alemán I. Astrocyte resilience to oxidative stress induced by insulin-like growth factor I (IGF-I) involves preserved AKT (protein kinase B) activity. J Biol Chem 2016, 291(5): 2510-2523.
Atalaia A, de Carvalho M, Evangelista T, et al. Sleep characteristics of amyotrophic lateral sclerosis in patients with preserved diaphragmatic function. Amyotroph Lateral Scler 2007, 8(2): 101-105.
Carratù P, Cassano A, Gadaleta F, et al. Association between low sniff nasal-inspiratory pressure (SNIP) and sleep disordered breathing in amyotrophic lateral sclerosis: Preliminary results. Amyotroph Lateral Scler 2011, 12(6): 458-463.
Iber C, Ancoli-Israel S, Chesson A, et al. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specification. 1st ed. Westchester: American Academy of Sleep Medicine, 2007, pp 134-137.
Arnulf I, Similowski T, Salachas F, et al. Sleep disorders and diaphragmatic function in patients with amyotrophic lateral sclerosis. Am J Respir Crit Care Med 2000, 161(3 Pt 1): 849-856.
Vrijsen B, Testelmans D, Belge C, et al. Non- invasive ventilation in amyotrophic lateral sclerosis. Amyotroph La Scl Fr 2013, 14(2): 85-95.
Anafi RC, Kayser MS, Raizen DM. Exploring phylogeny to find the function of sleep. Nat Rev Neurosci 2019, 20(2): 109-116.
Fultz NE, Bonmassar G, Setsompop K, et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science 2019, 366(6465): 628-631.
Irwin MR. Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol 2019, 19(11): 702-715.
Bellemsi M, de Vivo L, Chini M, et al. Sleep loss promotes astrocytic phagocytosis and microglial activation in mouse cerebral cortex. J Neurosci 2017, 37(21): 5263-5273.
Bakour C, Schwartz S, O’Rourke K, et al. Sleep duration trajectories and systemic inflammation in young adults: results from the national longitudinal study of adolescent to adult health (add health). Sleep 2017, 40(11): zsx156.
Maurovich-Horvat E, Pollmächer TZ, Sonka K. The effects of sleep and sleep deprivation on metabolic, endocrine and immune parameters. Prague Med Rep 2008, 109(4): 275-285.
Piovezan RD, Abucham J, Dos Santos RV, et al. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications. Ageing Res Rev 2015, 23(Pt B): 210-220.
Sifringer M, von Haefen C, Krain M, et al. Neuroprotective effect of dexmedetomidine on hyperoxia-induced toxicity in the neonatal rat brain. Oxid Med Cell Longev 2015, 2015: 530371.
Wang SL, Duan L, Xia B, et al. Dexmedetomidine preconditioning plays a neuroprotective role and suppresses TLR4/NF-κB pathways model of cerebral ischemia reperfusion. Biomed Pharmacother 2017, 93: 1337-1342.
An JX, Williams JP, Fang QW, et al. Feasibility of patient-controlled sleep with dexmedetomidine in treating chronic intractable insomnia. Nat Sci Sleep 2020, 12: 1033-1042.
Akeju O, Hobbs, LE Gao, et al. Dexmedetomidine promotes biomimetic non-rapid eye movement stage 3 sleep in humans: A pilot study. Clin Neurophysiol 2018, 129(1): 69-78.
Alexopoulou C, Kondili E, Diamantaki E, et al. Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study. Anesthesiology 2014, 121(4): 801-807.
Gerashchenko D, Pasumarthi RK, Kilduff TS. Plasticity-related gene expression during eszopiclone- induced sleep. Sleep 2017, 40(7): zsx098.
Kurian KM, Forbes RB, Colville S, et al. Cause of death and clinical grading criteria in a cohort of amyotrophic lateral sclerosis cases undergoing autopsy from the Scottish Motor Neurone Disease Register. J Neurol Neurosurg Psychiatry 2009, 80(1): 84-87.
Neudert C, Wasner M, Borasio GD. Individual quality of life is not correlated with health-related quality of life or physical function in patients with amyotrophic lateral sclerosis. J Palliat Med 2004, 7(4): 551-557.
Drevets WC, Furey ML. Replication of scopolamine's antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry 2010, 67(5): 432-438.
Brain Science Advances
Pages 155-162
Cite this article:
Cai Q, Li M, Li Q. Sleep-based therapy: A new treatment for amyotrophic lateral sclerosis. Brain Science Advances, 2021, 7(3): 155-162.








Received: 06 January 2021
Revised: 03 June 2021
Accepted: 04 June 2021
Published: 08 December 2021
© The authors 2021

This article is published with open access at

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (