Unraveling the Role of Mitochondria in Alzheimer’s Disease

2020 ◽  
pp. 407-430
Author(s):  
Sónia C. Correia ◽  
Paula I. Moreira ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Scientific Community ◽  
Future Research ◽  
Mitochondrial Bioenergetics ◽  
Limited Knowledge ◽  
Comprehensive Picture ◽  
Mitochondrial Defects

Alzheimer’s disease (AD) is an intriguing and still unsolved puzzle that has attracted, over the last decades, the interest of the scientific community. Despite the limited knowledge regarding the initial cause(s) of AD, mitochondrial abnormalities have been pinpointed as one of the earliest and strongest events related with the pathological course of this complex neurodegenerative disease. In this sense, the present chapter addresses three distinct but connected pieces of the AD puzzle: (a) how could defects of mitochondrial bioenergetics and dynamics contribute to AD pathology? (b) Could mitochondrial defects promote the disease-defining amyloid-β‎ and tau pathologies, and vice versa? and (c) Are mitochondria feasible therapeutic targets to postpone AD symptomatology and neuropathology, and, if so, how and when? The understanding and connection of these puzzle pieces provide a more comprehensive picture about the fundamental role of mitochondrial (mal)function in the neurodegenerative processes that occur in AD and propels future research interventions aimed to forestall AD-related pathological phenotype by bolstering mitochondrial “health.”

scholarly journals Role of the Extracellular Matrix in Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Yahan Sun ◽  
Sen Xu ◽  
Ming Jiang ◽  
Xia Liu ◽  
Liang Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Extracellular Matrix ◽  
Neurodegenerative Disease ◽  
Protein Production ◽  
Amyloid Β ◽  
Pathological Process ◽  
Future Research ◽  
The Past

Alzheimer’s disease (AD) is a neurodegenerative disease with complex pathological characteristics, whose etiology and pathogenesis are still unclear. Over the past few decades, the role of the extracellular matrix (ECM) has gained importance in neurodegenerative disease. In this review, we describe the role of the ECM in AD, focusing on the aspects of synaptic transmission, amyloid-β-plaque generation and degradation, Tau-protein production, oxidative-stress response, and inflammatory response. The function of ECM in the pathological process of AD will inform future research on the etiology and pathogenesis of AD.

scholarly journals Overview of Alzheimer’s Disease and Some Therapeutic Approaches Targeting Aβby Using Several Synthetic and Herbal Compounds

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Sandeep Kumar Singh ◽  
Saurabh Srivastav ◽  
Amarish Kumar Yadav ◽  
Saripella Srikrishna ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Neurodegenerative Disease ◽  
Therapeutic Approaches ◽  
Age Related

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease. In this review, we carefully detail amyloid-βmetabolism and its role in AD. We also consider the various genetic animal models used to evaluate therapeutics. Finally, we consider the role of synthetic and plant-based compounds in therapeutics.

scholarly journals Potential Role of Phenolic Extracts of Mentha in Managing Oxidative Stress and Alzheimer’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 631
Author(s):  
Doaa M. Hanafy ◽  
Geoffrey E. Burrows ◽  
Paul D. Prenzler ◽  
Rodney A. Hill
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Potential Role ◽  
The Elderly ◽  
Future Research ◽  
Phenolic Constituents ◽  
The Central Nervous System ◽  
Developed Nations

With an increase in the longevity and thus the proportion of the elderly, especially in developed nations, there is a rise in pathological conditions that accompany ageing, such as neurodegenerative disorders. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory decline. The pathophysiology of the disease is poorly understood, with several factors contributing to its development, such as oxidative stress, neuroinflammation, cholinergic neuronal apoptotic death, and the accumulation of abnormal proteins in the brain. Current medications are only palliative and cannot stop or reverse the progression of the disease. Recent clinical trials of synthetic compounds for the treatment of AD have failed because of their adverse effects or lack of efficacy. Thus, there is impetus behind the search for drugs from natural origins, in addition to the discovery of novel, conventional therapeutics. Mints have been used traditionally for conditions relevant to the central nervous system. Recent studies showed that mint extracts and/or their phenolic constituents have a neuroprotective potential and can target multiple events of AD. In this review, we provide evidence of the potential role of mint extracts and their derivatives as possible sources of treatments in managing AD. Some of the molecular pathways implicated in the development of AD are reviewed, with focus on apoptosis and some redox pathways, pointing to mechanisms that may be modulated for the treatment of AD, and the need for future research invoking knowledge of these pathways is highlighted.

scholarly journals Choroidal Proteins Involved in Cerebrospinal Fluid Production may be Potential Drug Targets for Alzheimer's Disease Therapy

2011 ◽  
Vol 5 ◽  
pp. PMC.S6509 ◽  
Author(s):  
Peter Wostyn ◽  
Kurt Audenaert ◽  
Peter Paul De Deyn
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Late Onset ◽  
Future Research ◽  
Caffeine Consumption ◽  
Research Attention ◽  
Fluid Production ◽  
Β Amyloid

Alzheimer's disease is known to be the most common form of dementia in the elderly. It is clinically characterized by impairment of cognitive functions, as well as changes in personality, behavioral disturbances and an impaired ability to perform activities of daily living. To date, there are no effective ways to cure or reverse the disease. Genetic studies of early-onset familial Alzheimer's disease cases revealed causative mutations in the genes encoding β-amyloid precursor protein and the γ-secretase-complex components presenilin-1 and presenilin-2, supporting an important role of β-amyloid in the pathogenesis of Alzheimer's disease. Compromised function of the choroid plexus and defective cerebrospinal fluid production and turnover, with diminished clearance of β-amyloid, may play an important role in late-onset forms of Alzheimer's disease. If reduced cerebrospinal fluid turnover is a risk factor for Alzheimer's disease, then therapeutic strategies to improve cerebrospinal fluid flow are reasonable. However, the role of deficient cerebrospinal fluid dynamics in Alzheimer's disease and the relevance of choroidal proteins as potential therapeutic targets to enhance cerebrospinal fluid turnover have received relatively little research attention. In this paper, we discuss several choroidal proteins, such as Na+-K+ ATPase, carbonic anhydrase, and aquaporin 1, that may be targets for pharmacological up-regulation of cerebrospinal fluid formation. The search for potentially beneficial drugs useful to ameliorate Alzheimer's disease by facilitating cerebrospinal fluid production and turnover may be an important area for future research. However, the ultimate utility of such modulators in the management of Alzheimer's disease remains to be determined. Here, we hypothesize that caffeine, the most commonly used psychoactive drug in the world, may be an attractive therapeutic candidate for treatment of Alzheimer's disease since long-term caffeine consumption may augment cerebrospinal fluid production. Other potential mechanisms of cognitive protection by caffeine have been suggested by recent studies.

scholarly journals MicroRNAs and Alzheimer's Disease Mouse Models: Current Insights and Future Research Avenues

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Charlotte Delay ◽  
Sébastien S. Hébert
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Animal Models ◽  
Mouse Models ◽  
Future Research ◽  
Neuronal Function ◽  
Key Genes

Evidence from clinical trials as well as from studies performed in animal models suggest that both amyloid and tau pathologies function in concert with other factors to cause the severe neurodegeneration and dementia in Alzheimer’s disease (AD) patients. Accumulating data in the literature suggest that microRNAs (miRNAs) could be such factors. These conserved, small nonprotein-coding RNAs are essential for neuronal function and survival and have been implicated in the regulation of key genes involved in genetic and sporadic AD. The study of miRNA changes in AD mouse models provides an appealing approach to address the cause-consequence relationship between miRNA dysfunction and AD pathology in humans. Mouse models also provide attractive tools to validate miRNA targetsin vivoand provide unique platforms to study the role of specific miRNA-dependent gene pathways in disease. Finally, mouse models may be exploited for miRNA diagnostics in the fight against AD.

scholarly journals Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease

2020 ◽  
Vol 21 (8) ◽  
pp. 2749
Author(s):  
Michał Wiciński ◽  
Anna Domanowska ◽  
Eryk Wódkiewicz ◽  
Bartosz Malinowski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
State Of The Art ◽  
Therapeutic Option ◽  
The State ◽  
Future Research ◽  
Disease Treatment ◽  
Research Results

The lack of effective Alzheimer’s disease treatment is becoming a challenge for researchers and prompts numerous attempts to search for and develop better therapeutic solutions. Compounds that affect several routes of the neurodegeneration cascade leading to the development of disease are of particular interest. An example of such substances is resveratrol and its synthetic and natural derivatives, which have gained popularity in recent years and show promise as a possible new therapeutic option in the approach to Alzheimer’s disease treatment. In this article, the state of the art evidence on the role of resveratrol (RSV) in neuroprotection is presented; research results are summarized and the importance of resveratrol and its derivatives in the treatment of Alzheimer’s disease are underlined. It also focuses on various modifications of the resveratrol molecule that should be taken into account in the design of future research on drugs against Alzheimer’s disease.

scholarly journals Significance of Hypouricaemia in the Development of Neurodegenerative Diseases

2021 ◽  
Vol 75 (2) ◽  
pp. 92-98
Author(s):  
Maximiliane Trapp ◽  
Anna Mihailova ◽  
Natalija Kakurina ◽  
Modra Murovska
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Uric Acid ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Vascular Dementia ◽  
Neuroprotective Effect ◽  
Significant Difference ◽  
Potential Risks

Abstract Hypouricaemia has received relatively little attention in the literature. As a result, there is less awareness or understanding of the potential risks of low uric acid levels. Emerging research indicates that normal uric acid levels may have an antioxidative and neuroprotective effect. This study aims to investigate possible associations between hypouricaemia and neurodegenerative disease. Data was collected from seventy-seven outpatients and inpatients who underwent routine uric acid testing, who were then stratified into patients with and without neurodegenerative disease. Patients with renal pathologies and patients using uric acid altering medications were excluded from the study. There was a significant difference in the prevalence of Alzheimer’s disease between hypouricemic and normouricemic patients (p = 0.001), however there was no difference in the prevalence of vascular dementia (p = 0.45). This study provides evidence that hypouricaemia has potential effects on health, specifically on the rate of neurodegenerative diseases such as Alzheimer’s disease and gives weight to the potential neuroprotective role of uric acid.

scholarly journals The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Linlin Zhang ◽  
Aurelio Reyes ◽  
Xiangdong Wang
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disease ◽  
And Oxidative Stress

The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondria-targeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function.

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