The Antiapoptotic Activity of Melatonin in Neurodegenerative Diseases

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2009 Oct 13

PMID 19818070

Citations 81

Authors

Xin Wang

Affiliations

Soon will be listed here.

Abstract

Melatonin plays a neuroprotective role in models of neurodegenerative diseases. However, the molecular mechanisms underlying neuroprotection by melatonin are not well understood. Apoptotic cell death in the central nervous system is a feature of neurodegenerative diseases. The intrinsic and extrinsic apoptotic pathways and the antiapoptotic survival signal pathways play critical roles in neurodegeneration. This review summarizes the reports to date showing inhibition by melatonin of the intrinsic apoptotic pathways in neurodegenerative diseases including stroke, Alzheimer disease, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis. Furthermore, the activation of survival signal pathways by melatonin in neurodegenerative diseases is discussed.

Citing Articles

Melatonin effects on animal behavior: circadian rhythm, stress response, and modulation of behavioral patterns.

Song Y, Yoon M J Anim Sci Technol. 2025; 67(1):1-16.

PMID: 39974791 PMC: 11833209. DOI: 10.5187/jast.2024.e105.

Melatonin ameliorates astrogliosis and microgliosis in a cuprizone demyelinating mouse model.

Alidadi M, Omidi N, Abdi M, Mohammadi M, Shabani M, Kashani I Biochem Biophys Rep. 2025; 41:101929.

PMID: 39926210 PMC: 11803163. DOI: 10.1016/j.bbrep.2025.101929.

The Melatonin Type 2 Receptor Agonist IIK7 Attenuates and Reverses Morphine Tolerance in Neuropathic Pain Rats Through the Suppression of Neuroinflammation in the Spinal Cord.

Kuthati Y, Wong C Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770480 PMC: 11676719. DOI: 10.3390/ph17121638.

Oxidative/Nitrosative Stress and Brain Involvement in Sepsis: A Relationship Supported by Immunohistochemistry.

Bertozzi G, Ferrara M, Calvano M, Pascale N, Di Fazio A Medicina (Kaunas). 2025; 60(12.

PMID: 39768830 PMC: 11678000. DOI: 10.3390/medicina60121949.

Melatonin improves cognitive dysfunction and decreases gliosis in the streptozotocin-induced rat model of sporadic Alzheimer's disease.

Gall Z, Boros B, Kelemen K, Urkon M, Zolcseak I, Marton K Front Pharmacol. 2024; 15:1447757.

PMID: 39135795 PMC: 11317391. DOI: 10.3389/fphar.2024.1447757.

References

Andrabi S, Sayeed I, Siemen D, Wolf G, Horn T . Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J. 2004; 18(7):869-71. DOI: 10.1096/fj.03-1031fje. View

Lee B, Lee D, Cho K, Kim G . Early nuclear translocation of endonuclease G and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Neurosci Lett. 2005; 386(1):23-7. DOI: 10.1016/j.neulet.2005.05.058. View

Feng Z, Qin C, Chang Y, Zhang J . Early melatonin supplementation alleviates oxidative stress in a transgenic mouse model of Alzheimer's disease. Free Radic Biol Med. 2005; 40(1):101-9. DOI: 10.1016/j.freeradbiomed.2005.08.014. View

Gonzalez-Burgos I, Cervantes M . Neuroprotective effect of melatonin on brain damage induced by acute global cerebral ischemia in cats. Arch Med Res. 2001; 32(3):186-92. DOI: 10.1016/s0188-4409(01)00268-5. View

Iqbal K, Alonso A, El-Akkad E, Gong C, Haque N, Khatoon S . Pharmacological targets to inhibit Alzheimer neurofibrillary degeneration. J Neural Transm Suppl. 2002; (62):309-19. DOI: 10.1007/978-3-7091-6139-5_29. View

Koh P . Melatonin attenuates the focal cerebral ischemic injury by inhibiting the dissociation of pBad from 14-3-3. J Pineal Res. 2007; 44(1):101-6. DOI: 10.1111/j.1600-079X.2007.00495.x. View

Medeiros C, de Bruin P, Lopes L, Magalhaes M, de Lourdes Seabra M, de Bruin V . Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson's disease. A randomized, double blind, placebo-controlled study. J Neurol. 2007; 254(4):459-64. DOI: 10.1007/s00415-006-0390-x. View

Iacovitti L, Stull N, Johnston K . Melatonin rescues dopamine neurons from cell death in tissue culture models of oxidative stress. Brain Res. 1997; 768(1-2):317-26. DOI: 10.1016/s0006-8993(97)00668-9. View

Jin Z, El-Deiry W . Overview of cell death signaling pathways. Cancer Biol Ther. 2005; 4(2):139-63. DOI: 10.4161/cbt.4.2.1508. View

10.

Kilic U, Kilic E, Reiter R, Bassetti C, Hermann D . Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice. J Pineal Res. 2004; 38(1):67-71. DOI: 10.1111/j.1600-079X.2004.00178.x. View

11.

Asayama K, Yamadera H, Ito T, Suzuki H, Kudo Y, Endo S . Double blind study of melatonin effects on the sleep-wake rhythm, cognitive and non-cognitive functions in Alzheimer type dementia. J Nippon Med Sch. 2003; 70(4):334-41. DOI: 10.1272/jnms.70.334. View

12.

Deigner H, Haberkorn U, Kinscherf R . Apoptosis modulators in the therapy of neurodegenerative diseases. Expert Opin Investig Drugs. 2000; 9(4):747-64. DOI: 10.1517/13543784.9.4.747. View

13.

Feng Z, Cheng Y, Zhang J . Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. J Pineal Res. 2004; 37(3):198-206. DOI: 10.1111/j.1600-079X.2004.00158.x. View

14.

Sas K, Robotka H, Toldi J, Vecsei L . Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci. 2007; 257(1-2):221-39. DOI: 10.1016/j.jns.2007.01.033. View

15.

Tunez I, Montilla P, Del Carmen Munoz M, Feijoo M, Salcedo M . Protective effect of melatonin on 3-nitropropionic acid-induced oxidative stress in synaptosomes in an animal model of Huntington's disease. J Pineal Res. 2004; 37(4):252-6. DOI: 10.1111/j.1600-079X.2004.00163.x. View

16.

Sewerynek E . Melatonin and the cardiovascular system. Neuro Endocrinol Lett. 2002; 23 Suppl 1:79-83. View

17.

Xie J, Awad K, Guo Q . RNAi knockdown of Par-4 inhibits neurosynaptic degeneration in ALS-linked mice. J Neurochem. 2004; 92(1):59-71. DOI: 10.1111/j.1471-4159.2004.02834.x. View

18.

Chetsawang B, Govitrapong P, Ebadi M . The neuroprotective effect of melatonin against the induction of c-Jun phosphorylation by 6-hydroxydopamine on SK-N-SH cells. Neurosci Lett. 2004; 371(2-3):205-8. DOI: 10.1016/j.neulet.2004.08.068. View

19.

Ryu H, Smith K, Camelo S, Carreras I, Lee J, Iglesias A . Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. J Neurochem. 2005; 93(5):1087-98. DOI: 10.1111/j.1471-4159.2005.03077.x. View

20.

Ravindra T, Lakshmi N, Ahuja Y . Melatonin in pathogenesis and therapy of cancer. Indian J Med Sci. 2006; 60(12):523-35. View