Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its Possible Therapeutic Potential in Alzheimer's Disease.

Abstract:

:Dimebon (latrepirdine), an old antihistaminic drug, showed divergent results in two large clinical trials in Alzheimer disease (AD), which according to our review might be related to the specific pharmacological properties of the drug and the different patient populations included in both studies. Out of the many pharmacological effects of Dimebon, improvement of impaired mitochondrial function seeems to be most relevant for the substantial effects on cognition and behaviour reported in one of the studies, as these effects are already present at the low concentrations of dimebon measured in plasma and tissues of patients and experimental animals. Since impaired mitochondrial function seems to be the major driving force for the progression of the clinical symptoms and since most of the clinical benefits of dimebon originate from an effect on the symptomatic deterioration, mitochondrial improvement can also explain the lack of efficacy of this drug in another clinical trial where symptoms of the patiets remained stable for the time of the study. Accordingly, it seems worthwhile to reevaluate the clinical data to proof that clinical response is correlated with high levels of Neuropsychiatric Symptoms as these show a good relationship to the individual speed of symptomatic decline in AD patients related to mitochondrial dysfunction.

journal_name

Aging Dis

journal_title

Aging and disease

authors

Eckert SH,Gaca J,Kolesova N,Friedland K,Eckert GP,Muller WE

doi

10.14336/AD.2017.1014

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

729-744

issue

4

issn

2152-5250

pii

ad-9-4-729

journal_volume

9

pub_type

杂志文章,评审
  • Diagnostic and Immunosuppressive Potential of Elevated Mir-424 Levels in Circulating Immune Cells of Ischemic Stroke Patients.

    abstract::Our previous study demonstrated that microRNA-424 (miR-424) protected against experimental stroke through inhibition of microglial proliferation and activation by targeting cell cycle proteins. The purpose of this study was to further explore the clinical significance of miR-424 in peripheral immune cells of patients ...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2017.0602

    authors: Li G,Ma Q,Wang R,Fan Z,Tao Z,Liu P,Zhao H,Luo Y

    更新日期:2018-04-01 00:00:00

  • Functional Dedifferentiation and Altered Connectivity in Older Adults: Neural Accounts of Cognitive Aging.

    abstract::Aging is associated with myriad changes in behavioral performance and brain structure and function. Given this complex interplay of brain and behavior, two streams of findings are reviewed here that show that aging is generally associated with dedifferentiated neural processes, and also changes in functional connectiv...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:

    authors: Goh JO

    更新日期:2011-01-01 00:00:00

  • Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity.

    abstract::Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severit...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2015.0906

    authors: Hu H,Doll DN,Sun J,Lewis SE,Wimsatt JH,Kessler MJ,Simpkins JW,Ren X

    更新日期:2016-01-02 00:00:00

  • The Critical Role of SIRT1 in Parkinson's Disease: Mechanism and Therapeutic Considerations.

    abstract::Silence information regulator 1 (SIRT1), a member of the sirtuin family, targets histones and many non-histone proteins and participates in various physiological functions. The enzymatic activity of SIRT1 is decreased in patients with Parkinson's disease (PD), which may reduce their ability to resist neuronal damage c...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2020.0216

    authors: Li X,Feng Y,Wang XX,Truong D,Wu YC

    更新日期:2020-12-01 00:00:00

  • Olfactory Dysfunction and Its Relationship with Clinical Symptoms of Alzheimer Disease.

    abstract::Our study aimed to analyse the olfactory dysfunction (OD) evaluations between self-report, the Hyposmia Rating Scale (HRS) and the Sniffin' Sticks test, and the relationship between OD and clinical features of AD. Sixty patients with AD dementia, 37 patients with mild cognitive impairment (MCI) due to AD and 30 health...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2018.0819

    authors: Yu Q,Guo P,Li D,Zuo L,Lian T,Yu S,Hu Y,Liu L,Jin Z,Wang R,Piao Y,Li L,Wang X,Zhang W

    更新日期:2018-12-04 00:00:00

  • Serum Zonulin and Endotoxin Levels in Exceptional Longevity versus Precocious Myocardial Infarction.

    abstract::Endotoxemia-induced inflammation has been associated with insulin resistance and atherosclerosis, ultimately increasing the risk of coronary heart disease. Increased intestinal permeability is an important event leading to endotoxemia. This study aims to elucidate the possible association between endotoxin (lipopolysa...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2017.0630

    authors: Carrera-Bastos P,Picazo Ó,Fontes-Villalba M,Pareja-Galeano H,Lindeberg S,Martínez-Selles M,Lucia A,Emanuele E

    更新日期:2018-04-01 00:00:00

  • mTOR Signaling from Cellular Senescence to Organismal Aging.

    abstract::The TOR (target of rapamycin) pathway has been convincingly shown to promote aging in various model organisms. In mice, inhibiting mTOR (mammalian TOR) by rapamycin treatment later in life can significantly extend lifespan and mitigate multiple age-related diseases. However, the underlying mechanisms are poorly unders...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2014.0500263

    authors: Xu S,Cai Y,Wei Y

    更新日期:2013-12-05 00:00:00

  • Alteration of Metabolic Profile and Potential Biomarkers in the Plasma of Alzheimer's Disease.

    abstract::The expending of elderly population worldwide has resulted in a dramatic rise in the incidence of chronic diseases such as Alzheimer's disease (AD). Inadequate understanding of the mechanisms underlying AD has hampered the development of efficient tools for definitive diagnosis and curative interventions. Previous stu...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2020.0217

    authors: Shao Y,Ouyang Y,Li T,Liu X,Xu X,Li S,Xu G,Le W

    更新日期:2020-12-01 00:00:00

  • Finding Balance: T cell Regulatory Receptor Expression during Aging.

    abstract::Aging is associated with a variety of changes to immune responsiveness. Reduced protection against infection, reduced responses to vaccination and increased risk of autoimmunity are all hallmarks of advanced age. Here we consider how changes in the expression of regulatory receptors on the T cell surface contribute to...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:

    authors: Cavanagh MM,Qi Q,Weyand CM,Goronzy JJ

    更新日期:2011-10-01 00:00:00

  • The effects of aging and electrical stimulation exercise on bone after spinal cord injury.

    abstract::Age related bone loss predisposes adults to osteoporosis. This is especially true for individuals with spinal cord injury (SCI). The effects of decreased bone loading with older age and paralysis significantly contribute to decreased bone mass and increased risk for fragility fractures. Loading bone via volitional mus...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:

    authors: Dolbow JD,Dolbow DR,Gorgey AS,Adler RA,Gater DR

    更新日期:2013-02-07 00:00:00

  • Prebiotics Regulation of Intestinal Microbiota Attenuates Cognitive Dysfunction Induced by Surgery Stimulation in APP/PS1 Mice.

    abstract::Emerging evidence indicates that the intestinal microbiota could interact with the central nervous system and modulate multiple pathophysiological changes, including the integrity of intestinal barrier and blood-brain barrier, as well as neuroinflammatory response. In the present study, we investigated the potential r...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2020.0106

    authors: Han D,Li Z,Liu T,Yang N,Li Y,He J,Qian M,Kuang Z,Zhang W,Ni C,Guo X

    更新日期:2020-10-01 00:00:00

  • Age-related defects in erythrocyte 2,3-diphosphoglycerate metabolism in dementia.

    abstract::Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the p...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2013.0400244

    authors: Kaminsky YG,Reddy VP,Ashraf GM,Ahmad A,Benberin VV,Kosenko EA,Aliev G

    更新日期:2013-10-01 00:00:00

  • Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment.

    abstract::Melatonin is a pleiotropically acting regulator molecule, which influences numerous physiological functions. Its secretion by the pineal gland progressively declines by age. Strong reductions of circulating melatonin are also observed in numerous disorders and diseases, including Alzheimer's disease, various other neu...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:

    authors: Hardeland R

    更新日期:2012-04-01 00:00:00

  • Serum Homocysteine, Dehydroepiandrosterone Sulphate and Lipoprotein (a) in Alzheimer's Disease and Vascular Dementia.

    abstract::Alzheimer's disease (AD) and vascular dementia (VAD) are the major forms of dementia affecting elderly people, in which the levels of many metabolites are altered in cerebrospinal fluid (CSF) and serum. These metabolites could be risk factors or potential biomarkers, but the significance of some of these are not clear...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:

    authors: Ray L,Khemka VK,Behera P,Bandyopadhyay K,Pal S,Pal K,Basu D,Chakrabarti S

    更新日期:2013-03-07 00:00:00

  • Relationship between CYP17A1 Genetic Polymorphism and Essential Hypertension in a Chinese Population.

    abstract::The relationship between CYP17A1 genetic polymorphisms and essential hypertension (EH) remains unclear. The aim of this study was to investigate the association of CYP17A1 genetic polymorphisms with EH in Han and Uighur populations in China. A Han population including 558 people (270 EH patients and 288 controls) and ...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2015.0505

    authors: Dai CF,Xie X,Ma YT,Yang YN,Li XM,Fu ZY,Liu F,Chen BD,Gai MT

    更新日期:2015-11-17 00:00:00

  • Predictive Value of Pin1 in Cervical Low-Grade Squamous Intraepithelial Lesions and Inhibition of Pin1 Exerts Potent Anticancer Activity against Human Cervical Cancer.

    abstract::Many oncogenes are involved in the progression from low-grade squamous intraepithelial lesions (LSILs) to high-grade squamous intraepithelial lesions (HSILs); which greatly increases the risk of cervical cancer (CC). Thus, a reliable biomarker for risk classification of LSILs is urgently needed. The prolyl isomerase P...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2019.0415

    authors: Guo YT,Lu Y,Jia YY,Qu HN,Qi D,Wang XQ,Song PY,Jin XS,Xu WH,Dong Y,Liang YY,Quan CS

    更新日期:2020-02-01 00:00:00

  • DRAM is Involved in Hypoxia/Ischemia-Induced Autophagic Apoptosis in Hepatocytes.

    abstract::Liver hypoxia/ischemia injury leads to acute liver injury, delayed graft dysfunction, and failure during liver transplantation. Previous studies showed that autophagy is involved in liver hypoxia/ischemia injury. Our and others' studies have found that the damage-regulated autophagy modulator (DRAM) could induce the a...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2018.0210

    authors: Xu J,Zang Y,Liu D,Yang T,Wang J,Wang Y,Liu X,Chen D

    更新日期:2019-02-01 00:00:00

  • Cellular and Molecular Biomarkers Indicate Premature Aging in Pseudoxanthoma Elasticum Patients.

    abstract::The molecular processes of aging are very heterogenic and not fully understood. Studies on rare progeria syndromes, which display an accelerated progression of physiological aging, can help to get a better understanding. Pseudoxanthoma elasticum (PXE) caused by mutations in the ATP-binding cassette sub-family C member...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2019.0610

    authors: Tiemann J,Wagner T,Vanakker OM,van Gils M,Cabrera JB,Ibold B,Faust I,Knabbe C,Hendig D

    更新日期:2020-05-09 00:00:00

  • Roles of Biomarkers in Myocardial Fibrosis.

    abstract::Myocardial fibrosis is observed in various cardiovascular diseases and plays a key role in the impairment of cardiac function. Endomyocardial biopsy, as the gold standard for the diagnosis of myocardial fibrosis, has limitations in terms of clinical application. Therefore, biomarkers have been recommended for noninvas...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2020.0604

    authors: Ding Y,Wang Y,Zhang W,Jia Q,Wang X,Li Y,Lv S,Zhang J

    更新日期:2020-10-01 00:00:00

  • Suicide in the global chinese aging population: a review of risk and protective factors, consequences, and interventions.

    abstract::As one of the leading causes of death around the world, suicide is a global public health threat. In the Chinese population, suicides constitute one-fifth of all recorded suicides in the world. Despite the factual data on suicide rates, the understanding of various causal factors behind suicide, including risk and pro...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2014.0223

    authors: Dong X,Chang ES,Zeng P,Simon MA

    更新日期:2015-03-10 00:00:00

  • Disease Progression-Dependent Expression of CD200R1 and CX3CR1 in Mouse Models of Parkinson's Disease.

    abstract::Microglial activation is an important contributor to the pathogenesis of Parkinson's disease (PD). Microglia are tightly and efficiently regulated by immune checkpoints, including CD200-CD200R1 and CX3CL1-CX3CR1. Understanding the involvement of these checkpoints in disease progression provides important insights into...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2019.0615

    authors: Wang L,Liu Y,Yan S,Du T,Fu X,Gong X,Zhou X,Zhang T,Wang X

    更新日期:2020-03-09 00:00:00

  • Association between Coagulation Function and Cerebral Microbleeds in Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease.

    abstract::Cerebral microbleeds (CMBs), which indicate hemorrhage-prone disease, may associate with hemostatic abnormalities, but the association between CMBs and coagulation function is uncertain. We aimed to examine this possible association. The following coagulation function indicators were evaluated in 85 consecutive ischem...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2016.0715

    authors: Liu J,Wang D,Xiong Y,Liu B,Lin J,Zhang S,Wu B,Wei C,Liu M

    更新日期:2017-04-01 00:00:00

  • Failure of Elevating Calcium Induces Oxidative Stress Tolerance and Imparts Cisplatin Resistance in Ovarian Cancer Cells.

    abstract::Cisplatin is a commonly used chemotherapeutic drug, used for the treatment of malignant ovarian cancer, but acquired resistance limits its application. There is therefore an overwhelming need to understand the mechanism of cisplatin resistance in ovarian cancer, that is, ovarian cancer cells are insensitive to cisplat...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2016.0118

    authors: Ma L,Wang H,Wang C,Su J,Xie Q,Xu L,Yu Y,Liu S,Li S,Xu Y,Li Z

    更新日期:2016-05-27 00:00:00

  • The Potential Markers of Circulating microRNAs and long non-coding RNAs in Alzheimer's Disease.

    abstract::Alzheimer's disease (AD) is a neurodegenerative disorder and one of the leading causes of disability and mortality in the late life with no curative treatment currently. Thus, it is urgently to establish sensitive and non-invasive biomarkers for AD diagnosis, particularly in the early stage. Recently, emerging number ...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2018.1105

    authors: Zhao Y,Zhang Y,Zhang L,Dong Y,Ji H,Shen L

    更新日期:2019-12-01 00:00:00

  • Hip fractures in a geriatric population - rehabilitation based on patients needs.

    abstract::With an increased life expectancy in humans and thus an increase in the number of the elderly population, the frequency of hip fractures will rise as well. Aside from a higher incidence, hip fractures in a geriatric population is a significant problem due to the possible onset of severe and in some cases dramatic comp...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2014.0500177

    authors: Radosavljevic N,Nikolic D,Lazovic M,Jeremic A

    更新日期:2014-06-01 00:00:00

  • Searching for Factors Raising the Incidence of Metabolic Syndrome Among 45-60-Year-Old Women.

    abstract::Metabolic syndrome is an increasing health problem, whose pathogenesis may be associated with genetic factors. The main purpose of our study was to assess relationships between MetS and the presence of the FTO rs9939609, the MC4R rs17782313, and the PPAR-γ rs1801282 polymorphisms in 45-60-year-old women. The study inc...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2017.1027

    authors: Małgorzata S,Jacek B,Jerzy OA,Piotr C,Anna J,Elżbieta G

    更新日期:2018-10-01 00:00:00

  • The Effects of Baicalin and Baicalein on Cerebral Ischemia: A Review.

    abstract::Ischemic stroke, producing a high mortality and morbidity rate, is a common clinical disease. Enhancing the prevention and control of ischemic stroke is particularly important. Baicalin and its aglycon baicalein are flavonoids extracted from Scutellaria baicalensis, an important traditional Chinese herb. In recent yea...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2017.0829

    authors: Liang W,Huang X,Chen W

    更新日期:2017-12-01 00:00:00

  • Brain Atrophy, Anti-Smooth Muscle Antibody and Cognitive Impairment: An Association Study.

    abstract::Cortical atrophy, neuronal loss, beta-amyloid deposition, neuritic plaques, and neurofibrillary tangles are neuropathological key features in the Alzheimer's disease (AD). Antibodies against beta-amyloid, neurotransmitters, microvascular endothelium components and microglial cells have been detected in AD serum sugges...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2015.1124

    authors: Giulia P,Michele L,Andrea F,Grazia D,Filomena C,Francesco P,Leandro C,Maria U,Carolina G,Massimiliano C,Antonio G

    更新日期:2015-11-24 00:00:00

  • The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review.

    abstract::It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial im...

    journal_title:Aging and disease

    pub_type: 杂志文章,评审

    doi:10.14336/AD.2014.0500307

    authors: Famakin BM

    更新日期:2014-10-01 00:00:00

  • A Microcirculatory Theory of Aging.

    abstract::Aging is the progressive decline of physiological functions necessary for survival and reproduction. In gaining a better understanding of the inevitable aging process, the hope is to preserve, promote, or delay healthy aging through the treatment of common age-associated diseases. Although there are theories that try ...

    journal_title:Aging and disease

    pub_type: 杂志文章

    doi:10.14336/AD.2019.0315

    authors: Jin K

    更新日期:2019-06-01 00:00:00