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The putative use of lithium in alzheimer's disease

Morris, Gerwyn and Berk, Michael 2016, The putative use of lithium in alzheimer's disease, Current alzheimer research, vol. 13, no. 8, pp. 853-861, doi: 10.2174/1567205013666160219113112.

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Title The putative use of lithium in alzheimer's disease
Author(s) Morris, Gerwyn
Berk, MichaelORCID iD for Berk, Michael orcid.org/0000-0002-5554-6946
Journal name Current alzheimer research
Volume number 13
Issue number 8
Start page 853
End page 861
Total pages 9
Publisher Bentham Science Publishers
Place of publication Bussum, Netherlands
Publication date 2016
ISSN 1567-2050
1875-5828
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Neurosciences & Neurology
Alzheimer's disease
amyloid
beta tau
calcium
dementia
inflammation
iron
lithium
microglia
mitochondria
oxidative stress
phosphorylation
GLYCOGEN-SYNTHASE KINASE-3
AMYLOID-PRECURSOR-PROTEIN
CHAPERONE-MEDIATED AUTOPHAGY
OXIDATIVE STRESS PARAMETERS
UBIQUITIN-PROTEASOME SYSTEM
BLOOD MONONUCLEAR-CELLS
A-BETA
MITOCHONDRIAL DYSFUNCTION
BIPOLAR DISORDER
IN-VIVO
Summary Alzheimer`s disease is a progressive neurodegenerative illness characterized by the invariant existence of β-amyloid plaques and neurofibrillary tangles. Presently approved pharmaceutical approaches offer only marginal efficacy and as yet there is no effective treatment which reverses or arrests the disease. Thus far, drugs targeting any single aspect of disease pathology have proved to be a failure or at best provided very slight clinical benefit. The consistent failure of drugs targeting aspects of the Aβ cascade has questioned the causal role of this pathway. There is a growing appreciation that the pathogenesis of the illness is multifactorial with Amyloid Beta, Phosphorylated Tau (ptau), inflammation, mitochondrial dysfunction, calcium dyshomeostasis, heavy metal imbalances, and GSK-3 interact in a highly complex manner to provoke a selfsustaining spiraling cascade of pathology, driving disease progression. In the light of such complex pathology, the failure of drugs aimed a targeting single molecules is not surprising as such approaches are usually ineffective against other complex diseases with a multifactorial pathogenesis. Combination therapies or multi target drugs might be more effective in controlling such illnesses. The putative neuroprotective effects of Lithium are achieved via the positive modulation of numerous homeostatic mechanisms regulating autophagy, oxidative stress, inflammation, and mitochondrial dysfunction likely achieved by inhibiting GSK-3 and inositol-145 triphosphate. Data regarding efficacy in human trials and animal models of AD are mixed, but recent data using "microdose" lithium in mild cognitive impairment is encouraging, hence lithium could be a putative multi target treatment in these patients. However, additional well designed long-term trials are needed to confirm its efficacy and safety, given that long term use is necessary to achieve reasonable therapeutic benefit.
Language eng
DOI 10.2174/1567205013666160219113112
Field of Research 110319 Psychiatry (incl Psychotherapy)
1103 Clinical Sciences
1109 Neurosciences
Socio Economic Objective 920112 Neurodegenerative Disorders Related to Ageing
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Bentham Science Publishers
Persistent URL http://hdl.handle.net/10536/DRO/DU:30086678

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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