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Melatonin in Alzheimer’s Disease: Focus on Neuroprotective Role

  • Venkataramanujam SrinivasanEmail author
  • Edward C. Lauterbach
  • Charanjit Kaur
  • Asma Hayati Ahmad
  • Mahaneem Mohamed
  • Atul Prasad
  • Samuel D. Shillcutt
Chapter

Abstract

Alzheimer’s disease (AD) is characterized by a progressive loss of memory and cognitive function as well as behavioral and sleep disturbances including insomnia. The pathophysiology of AD has been attributed to oxidative stress-induced amyloid β-protein (Aβ) deposition. Abnormal tau protein, mitochondrial dysfunction, and protein hyperphosphorylation have been demonstrated in neural tissues of AD patients. AD patients exhibit severe sleep-wake disturbances associated with rapid cognitive decline and memory impairment. Optimally effective management of AD patients requires a drug that can arrest Aβ-induced neurotoxic effects and restore the disturbed sleep-wake rhythm with improvement in sleep quality. In this context, the pineal hormone melatonin has been demonstrated to be an effective antioxidant that can prevent Aβ-induced neurotoxic effects through a variety of mechanisms. Sleep deprivation itself produces oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, altered proteosomal processing, and abnormal activation of enzymes. Treating sleep disturbances is also necessary for preventing and arresting AD progression. Besides melatonin, use of melatonergic agonists such as ramelteon, agomelatine, and tasimelteon, which are now used clinically for treating insomnia and other sleep disorders, may also be beneficial in treating AD.

Keywords

Alzheimer’s disease Melatonin Amyloid-β protein Insomnia Antioxidant Sleep 

Abbreviations

AD

Alzheimer’s disease

apoE4

Apolipoprotein-E4

Amyloid β-protein

ATP

Adenosine-5′-triphosphate

BDNF

Brain-derived neurotrophic factor

CSF

Cerebrospinal fluid

CypD

Cyclophilin D

ETC

Electron transport chain

H2O2

Hydrogen peroxide

MDA

Malondialdehyde

mtPTP

Mitochondrial permeability transition pore

O2

Superoxide

PKA

Protein kinase

ROS

Reactive oxygen species

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Copyright information

© Springer India 2014

Authors and Affiliations

  • Venkataramanujam Srinivasan
    • 1
    • 2
    • 3
    Email author
  • Edward C. Lauterbach
    • 4
  • Charanjit Kaur
    • 5
  • Asma Hayati Ahmad
    • 6
  • Mahaneem Mohamed
    • 6
  • Atul Prasad
    • 7
  • Samuel D. Shillcutt
    • 8
  1. 1.Sri Sathya Sai Medical Educational and Research Foundation, An International Medical Sciences Research Study CenterCoimbatoreIndia
  2. 2.National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and TreatmentHospital “G. Mazzini”TeramoItaly
  3. 3.Department of Neuroscience and ImagingUniversity “G.D’ Annunzio”ChietiItaly
  4. 4.Department of Psychiatry and Behavioral Sciences, and the Department of Internal Medicine, Neurology SectionMercer University School of MedicineMaconUSA
  5. 5.Department of Anatomy, Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore
  6. 6.Department of PhysiologySchool of Medical Sciences, Universiti Sains MalaysiaKubang Kerian, KelantanMalaysia
  7. 7.Department of NeurologyDr BL Kapur Superspeciality HospitalNew DelhiIndia
  8. 8.Department of Psychiatry and Behavioral ScienceMercer University School of MedicineMaconUSA

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