A meta-analysis of mood stabilizers for Alzheimer’s disease

Xiao, Heng; Su, Ying; Cao, Xu; Sun, Shan; Liang, Zhihou

doi:10.1007/s11596-010-0559-5

Cited by 18 publications

(6 citation statements)

References 36 publications

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“…These findings are compatible with a study presenting that lysosomal acidification is malfunctioning in the PS1 knockout principal neurons and fibroblasts in Alzheimer's patients with PS1 mutations (Wolfe et al, 2013). Phase II (Forlenza et al, 2012Nicotinamide Between 1935and 1937 Improvement of autophagy-lysosome processing Phase I (D. Liu, Pitta, et al, 2013 Carbamazepine 1953 Antiepileptic Decrease mTOR activity Xiao, Su, Cao, Sun, and Liang (2010) BECN1 mimetics Autophagy regulator Initiation of autophagy and autophagosome clearance ) Haque, et al, 2016Uddin, Mamun, Takeda, Sarwar, & Begum, 2018). For successful treatment, degradation of toxic molecules is necessary.…”

Section: Ps Dysfunction and Autophagic-lysosomal System In Adsupporting

confidence: 81%

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Uddin

Mamun

Labu

et al. 2018

Journal Cellular Physiology

119

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Autophagy is a preserved cytoplasmic self‐degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy‐related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis.

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Section: Ps Dysfunction and Autophagic-lysosomal System In Adsupporting

confidence: 81%

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Uddin

Mamun

Labu

et al. 2018

Journal Cellular Physiology

119

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“…Carbamazepine was primarily developed as a drug used in the treatment of epilepsy ( Okuma and Kishimoto, 1998 ). In the past, scientists studied therapeutic effect of CBZ on AD-related agitation ( Xiao et al, 2010 ). Recently two publications have shown that carbamazepine-induced autophagy also protected against memory dysfunction and increase in Aβ content in brains of mouse model of AD ( Li et al, 2013 ; Zhang et al, 2017 ).…”

Section: Therapeutic Implications Of the Interplay Of Alzheimer’s Dismentioning

confidence: 99%

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

Uddin

Stachowiak

Mamun

et al. 2018

Front. Aging Neurosci.

317

247

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Alzheimer’s disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid β (Aβ), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aβ is dysregulated, which leads to the accumulation and aggregation of Aβ. Metabolism of Aβ and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.

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“…All of these therapeutic drugs exhibited positive effects on Aβ reduction and on alleviating AD symptoms. Nevertheless, a recent meta-analysis indicated that mood stabilizers such as CBZ and Rap were not effective but rather are harmful to AD patients [ 31 ]. More importantly, several issues in this study should be addressed by future researchers.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Effectiveness of GTM-1, Rapamycin, and Carbamazepine on Autophagy and Alzheimer Disease

Zhang

Wang

et al. 2017

Med Sci Monit

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BackgroundThis study was proposed to compare the efficacy and safety of GTM-1, Rapamycin (Rap), and Carbamazepine (CBZ) in managing Alzheimer disease (AD). The impact of the above mentioned therapeutic drugs on autophagy was also investigated in our study.Material/MethodsFirstly, 3×Tg AD mice were randomly allocated into 4 groups (each group with 10 mice), in which AD mice were separately treated with dimethylsulfoxide (DMSO, vehicle group), GTM-1 (6 mg/kg), Rap (1 mg/kg), and CBZ (100 mg/kg). Then spatial memory and learning ability of mice was tested using the Morris water maze. Routine blood tests were performed to evaluate the toxicity of these drugs. Amyloid-β42 (Aβ42) concentration was detected by ELISA and immunohistochemistry. Proteins related to autophagy were detected by Western blot.ResultsGTM-1, Rap, and CBZ significantly improved the spatial memory of 3×Tg AD mice compared to that in the vehicle group (all P<0.05). Moreover, this study revealed that CBZ dosage was related to toxicity in mice. All of the above drugs significantly increased the expression of LC3-II and reduced Aβ42 levels in hippocampi of 3×Tg AD mice (all P<0.05). On the other hand, neither GTM-1 nor CBZ had significant influence on the expression of proteins on the mTOR pathway.ConclusionsGTM-1 can alleviate the AD syndrome by activating autophagy in a manner that is dependent on the mTOR pathway and it therefore can be considered as an alternative to Rap.

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A meta-analysis of mood stabilizers for Alzheimer’s disease

Cited by 18 publications

References 36 publications

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Autophagic dysfunction in Alzheimer’s disease: Cellular and molecular mechanistic approaches to halt Alzheimer’s pathogenesis

Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

Evaluating the Effectiveness of GTM-1, Rapamycin, and Carbamazepine on Autophagy and Alzheimer Disease

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