Ketogenic diet: A promising neuroprotective composition for managing Alzheimer’s diseases and its pathological mechanisms

2021 ◽  
Vol 21 ◽  
Author(s):  
Badrinathan Sridharan ◽  
Meng-Jen Lee
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Energy Metabolism ◽  
Ketogenic Diet ◽  
Metabolic Diseases ◽  
Ketone Bodies ◽  
The Body ◽  
Research Progress ◽  
Therapeutic Action ◽  
Energy Deprivation

: Ketogenic diet and ketone bodies gained significant attention in recent years due to their ability to influence the specific energy metabolism and restoration of mitochondrial homeostasis that can help in hindering the progression of many metabolic diseases including diabetes and neurodegenerative diseases. Ketogenic diet consists of high fat and low carbohydrate contents which makes the body glucose deprived and rely on alternative sources (ketone bodies) for energy. It has been initially designed and supplemented for the treatment of epilepsy and later its influence on many energy-deriving biochemical pathways made it a highly sorted food supplement for many metabolic diseases and even by healthy individuals for body building and calorie restriction. Among the reported therapeutic action over a range of diseases, neurodegenerative disorders especially Alzheimer’s disease gained the attention of many researchers and clinicians because of its potency and its easier supplementation as a food additive. Complex pathology and multiple influencing factors of Alzheimer’s disease make exploration of its therapeutic strategies a demanding task. It was a common phenomenon that energy deprivation in neurological disorders including Alzheimer’s disease, to progress rapidly. The ability of ketone bodies to stabilize the mitochondrial energy metabolism makes it a suitable intervening agent. In this review, we will discuss various research progress made with regards to ketone bodies/ketogenic diet for management of Alzheimer’s disease and elaborate in detail about the mechanisms that are influenced during their therapeutic action.

scholarly journals Ketogenic Diet in Alzheimer’s Disease

2019 ◽  
Vol 20 (16) ◽  
pp. 3892 ◽  
Author(s):  
Marta Rusek ◽  
Ryszard Pluta ◽  
Marzena Ułamek-Kozioł ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ketogenic Diet ◽  
Neurodegenerative Disorder ◽  
Ketone Bodies ◽  
Amyloid Β ◽  
The Body ◽  
Aging Brain ◽  
Effective Prevention ◽  
Low Carbohydrate Diet

At present, the prevalence of Alzheimer’s disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer’s disease. This review aims to examine the role of the ketogenic diet in Alzheimer’s disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer’s disease.

scholarly journals Neuroprotection by the Ketogenic Diet: Evidence and Controversies

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah M. Gough ◽  
Alicia Casella ◽  
Kristen Jasmin Ortega ◽  
Abigail S. Hackam
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ketogenic Diet ◽  
Molecular Mechanisms ◽  
Ketone Bodies ◽  
Current Evidence ◽  
Pediatric Epilepsy ◽  
Low Carbohydrate Diet ◽  
Cord Injury

The ketogenic diet (KD) is a high-fat low-carbohydrate diet that has been used for decades as a non-pharmacologic approach to treat metabolic disorders and refractory pediatric epilepsy. In recent years, enthusiasm for the KD has increased in the scientific community due to evidence that the diet reduces pathology and improves various outcome measures in animal models of neurodegenerative disorders, including multiple sclerosis, stroke, glaucoma, spinal cord injury, retinal degenerations, Parkinson's disease and Alzheimer's disease. Clinical trials also suggest that the KD improved quality of life in patients with multiple sclerosis and Alzheimer's disease. Furthermore, the major ketone bodies BHB and ACA have potential neuroprotective properties and are now known to have direct effects on specific inflammatory proteins, transcription factors, reactive oxygen species, mitochondria, epigenetic modifications and the composition of the gut microbiome. Neuroprotective benefits of the KD are likely due to a combination of these cellular processes and other potential mechanisms that are yet to be confirmed experimentally. This review provides a comprehensive summary of current evidence for the effectiveness of the KD in humans and preclinical models of various neurological disorders, describes molecular mechanisms that may contribute to its beneficial effects, and highlights key controversies and current gaps in knowledge.

scholarly journals DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease

2021 ◽  
Vol 22 (13) ◽  
pp. 6748
Author(s):  
Heling Wang ◽  
Sofie Lautrup ◽  
Domenica Caponio ◽  
Jianying Zhang ◽  
Evandro F. Fang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Repair ◽  
Werner Syndrome ◽  
Accelerated Ageing ◽  
Genes Encoding ◽  
Group A ◽  
Group B ◽  
Novel Therapeutic Strategies ◽  
Energy Deprivation

DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB, respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM), and Werner syndrome (WS, with most cases caused by mutations in WRN). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD+), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer’s disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.

Alzheimer’s disease and its related Dementia types: A review on their management via nanotechnology based therapeutic strategies

2021 ◽  
Vol 18 ◽  
Author(s):  
Panoraia I. Siafaka ◽  
Gökce Mutlu ◽  
Neslihan Üstündağ Okur
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Vascular Dementia ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
The Body ◽  
Daily Routine ◽  
Mixed Dementia ◽  
The Brain

Background: Dementia and its related types such as Alzheimer’s disease, vascular dementia and mixed dementia belong to brain associated diseases, resulting in long-term progressive memory loss. These diseases are so severe that can affect a person's daily routine. Up to date, treatment of de- mentias is still an unmet challenge due to their complex pathophysiology and unavailable efficient pharmacological approaches. The use of nanotechnology based pharmaceutical products could possibly improve the management of dementia given that nanocarriers could more efficiently deliver drugs to the brain. Objective: The objective of this study is to provide the current nanotechnology based drug delivery systems for the treatment of various dementia types. In addition, the current diagnosis biomarkers for the mentioned dementia types along with their available pharmacological treatment are being dis- cussed. Method: An extensive review of the current nanosystems such as brain drug delivery systems against Alzheimer’s disease, vascular dementia and mixed dementia was performed. Moreover, nan- otheranostics as possible imaging markers for such dementias were also reported. Results: The field of nanotechnology is quite advantageous for targeting dementia given that nanoscale drug delivery systems easily penetrate the blood brain barrier and circulate in the body for prolonged time. These nanoformulations consist of polymeric nanoparticles, solid lipid nanoparticles, nanostruc- tured lipid carriers, microemulsions, nanoemulsions, and liquid crystals. The delivery of the nan- otherapeutics can be achieved via various administration routes such as transdermal, injectable, oral, and more importantly, through the intranasal route. Nonetheless, the nanocarriers are mostly limited to Alzheimer’s disease targeting; thus, nanocarriers for other types of dementia should be developed. Conclusion: To conclude, understanding the mechanism of neurodegeneration and reviewing the cur- rent drug delivery systems for Alzheimer’s disease and other dementia types are significant for medical and pharmaceutical society to produce efficient therapeutic choices and novel strategies based on mul- tifunctional and biocompatible nanocarriers, which can deliver the drug sufficiently into the brain.

Non-Ceruloplasmin Copper as a Stratification Biomarker of Alzheimer’s Disease Patients: How to Measure and Use It

2021 ◽  
Vol 18 ◽  
Author(s):  
Rosanna Squitti ◽  
Mariacarla Ventriglia ◽  
Alberto Granzotto ◽  
Stefano L. Sensi ◽  
Mauro Ciro Antonio Rongioletti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Cost Effective ◽  
The Elderly ◽  
The Body ◽  
Eligibility Criterion ◽  
Growing Body ◽  
Proper Balance

: Alzheimer’s disease (AD) is a type of dementia very common in the elderly. A growing body of recent evidence has linked AD pathogenesis to copper (Cu) dysmetabolism in the body. In fact, a subset of patients affected either by AD or by its prodromal form known as Mild Cognitive Impairment (MCI) have been observed to be unable to maintain a proper balance of Cu metabolism and distribution and are characterized by the presence in their serum of increased levels of Cu not bound to ceruloplasmin (non-ceruloplasmin Cu). Since serum non-ceruloplasmin Cu is a biomark- er of Wilson's disease (WD), a well-known condition of Cu-driven toxicosis, in this review, we pro- pose that in close analogy with WD, the assessment of non-ceruloplasmin Cu levels can be exploit- ed as a cost-effective stratification and susceptibility/risk biomarker for the identification of some AD/MCI individuals. The approach can also be used as an eligibility criterion for clinical trials aim- ing at investigating Cu-related interventions against AD/MCI.

scholarly journals Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP-CTFs in Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Senthilkumar Sivanesan ◽  
Ravi Mundugaru ◽  
Jayakumar Rajadas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ketone Bodies ◽  
Brain Regions ◽  
Pentose Phosphate ◽  
Lactate Shuttle ◽  
Carboxy Terminal ◽  
Brain Energy

Vascular dysfunctions, hypometabolism, and insulin resistance are high and early risk factors for Alzheimer’s disease (AD), a leading neurological disease associated with memory decline and cognitive dysfunctions. Early defects in glucose transporters and glycolysis occur during the course of AD progression. Hypometabolism begins well before the onset of early AD symptoms; this timing implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy to the starving AD brain, a considerable energy crisis still persists and increases during disease progression. Studies that track brain energy metabolism in humans, animal models of AD, and in vitro studies reveal striking upregulation of beta-amyloid precursor protein (β-APP) and carboxy-terminal fragments (CTFs). Currently, the precise role of CTFs is unclear, but evidence supports increased endosomal-lysosomal trafficking of β-APP and CTFs through autophagy through a vague mechanism. While intracellular accumulation of Aβ is attributed as both the cause and consequence of a defective endolysosomal-autophagic system, much remains to be explored about the other β-APP cleavage products. Many recent works report altered amino acid catabolism and expression of several urea cycle enzymes in AD brains, but the precise cause for this dysregulation is not fully explained. In this paper, we try to connect the role of CTFs in the energy translation process in AD brain based on recent findings.

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