Abnormal metal homeostasis as a common drug target to combat neurodegenerative diseases

正As life expectancy increases, the prevalence of age-related diseases will also increase. There has been an estimation that 50 million individuals are living with dementia in 2019. This number will increase to 75 million in 2030 and 131.5 million by 2050(McGill-Carter, 2020). Neurodegenerative diseases such as Alzheimer's disease(AD),     

How mind-body therapies might reduce pathological features of Alzheimer’s disease

Alzheimer’s disease(AD)is an irreversible neurodegenerat i ve disorder that i s responsible for around 60-80%of all dementia cases and currently affects around 50 million people worldwide.As the population’s life span tends to increase,current predictions suggest that by 2050,152 million people worldwide will suffer from dementia(Balsinha,2019).While the exact cause of AD remains obscure,various hypotheses regarding AD etiology have been described in the last decades.According to the amyloid hypothesis,the pathogenic changes related to AD start with the accumulation of amyloid-beta(Aβ)in the brain.These Aβpeptides form oligomers and insoluble amyloid plaques which are neurotoxic and trigger harmful downstream events such as the aggregation of the microtubule-associated protein Tau into neurofibrillary tangles,chronic inflammation,and brain atrophy.     

Gamma-aminobutyric acid A receptors in Alzheimer's disease: highly localized remodeling of a complex and diverse signaling pathway

正Alzheimer’s disease(AD),the predominant form of dementia,is a chronic,incurable neurodegenerative disorder presenting with symptoms includ-ing progressive memory loss and disturbed emotional state.It has been estimated that dementia affects over 47 million people worldwide(Prince et al.,2015),and with 60–80%of cases attributable to AD.The primary pathological hallmarks of AD are neuronal death,the deposition of insolu-ble amyloid-beta(Aβ)plaques,the accumulation of hyperphosphorylated tau neurofibrillary tangles(NFTs),and the widespread dysregulation of     

Mechanosensitivity of N-methyl-D-aspartate receptors (NMDAR) is the key through which amyloid beta oligomers activate them

Alzheimer’s disease(AD)is one of the major forms of dementia,accounting for 60 to 80%of the cases of dementia,affecting approximately 50 million people worldwide,which is why it has become an object of great interest in both the medical and social fields(Source:Alzheimer’s Association).One of the main histopathological hallmarks of AD is the formation and accumulation of senile plaques in the brain parenchyma,mainly composed by fibrillar aggregates of the amyloidβ(Aβ)peptide.This peptide is generated by the cleavage of the membrane protein named amyloidβprecursor protein,and its secretion in the extracellular space leads to its aggregation into amyloid fibrils.Various intermediates of this process of aggregation have been identified,and it was found that prefibrillar,soluble oligomeric forms of Aβare more likely to be the pathological species(Benilova et al.,2012).     

Therapeutic potential of alpha 5 subunit containing GABA_A receptors in Alzheimer's disease

正Alheimer's disease(AD) is a common neurodegenerative disorder and the leading cause of dementia. It has been estimated that over 50 million people worldwide were affected by dementia in 2019, and the prevalence of dementia is expected to double approximately once every 20 years(Govindpani et al., 2017). Most people who die with AD require high levels of care for long periods of time.     

Role of presynaptic calcium stores for neural network dysfunction in Alzheimer's disease

正Alzheimer’s disease(AD)is the most common form of dementia representing a major problem for public health.In 2017 there were an estimated 50 million patients worldwide and this number is expected to almost double every 20years,reaching 75 million in 2030 and 131.5 million in 2050(https://www.alz.co.uk/research/statistics).Clinically there are two forms of the disease:the     

Finding chemopreventatives to reduce amyloid beta in yeast

正Alzheimer’s disease(AD)is the most common form of age-related dementia with the latest report(World Alzheimer Report,2015)showing 46.8 million people are currently affected by dementia.That number is expected to double every 20 years unless there is effective therapeutic intervention.The 42 amino acid peptide known as amyloid beta(or Aβ)has been implicated as one of the main causative agents of AD after its discovery in plaques in 1985(Masters et al.,1985).Since     

Sex differences in Alzheimer's disease:an urgent research venue to follow

<正>Due to increasing life expectancy,the amount of people with dementia worldwide is expected to experience a substantial rise,with estimates indicating a growth from 55 million in 2019 to a staggering 139 million by the year 2050.Among the various forms of dementia.Alzheimer’s disease(AD) stands out as the predominant and most prevalent.According to the Alzheimer’s Association(No authors listed,2023),     

Leukocyte telomere length and plasma interleukin-1β and interleukin-18 levels in mild cognitive impairment and Alzheimer's disease: new biomarkers for diagnosis and disease progression?

正Alzheimer's disease and mild cognitive impairment biomarkers: Alzheimer's disease(AD) is a progressive neurodegenerative disease of advancing age.It affects around 47 million people in the world and the number is estimated to increase to 152 million by 2050.Someone develops dementia every three seconds and the current annual cost of dementia is estimated at US $1 trillion, a figure set to double by 2030(Alzheimer's Disease International, 2019).     

Targeting the guanine-based purinergic system in Alzheimer’s disease

<正>Alzheimer’s disease(AD)is the main cause of dementia worldwide and affects approximately 5%of people with 65 years or older.The estimated increase in the elderly population suggests that cases of AD will rise in the next years.AD is a neurodegenerative disease characterized mainly by synaptic and neuronal loss.Post-mortem analysis     

Insights from human sleep research on neural mechanisms of Alzheimer's disease

Alzheimer's disease(AD)is considered as the major cause of dementia and affects about 50 million people in world population,with an expected increase of 27%in the coming decades,as reported by the most recent AD statistics.The fast-growing empirical evidence is highlighting the close relationship between sleep and AD since the preclinical stage of the disease,pointing to an important role of sleep in the occurrence and progression of AD.     

On the interaction of a donepezil-huprine hybrid with synthetic membrane models

<正>Alzheimer’s disease is the most prevalent type of dementia today,discovered and described by Alois Alzheimer in 1907.According to the World Alzheimer Report 2021,75%of people with dementia worldwide are undiagnosed,equivalent to 41 million people (Gauthier et al.,2021).With each passing year,the number of people affected by these diseases is increasing,and the estimates of suffering from them in the future are growing.There are currently only four drugs used against Alzheimer’s disease:...     

Therapeutic Potential of Glucagon-Like Peptide-1 Cleavage Product for Alzheimer's Disease

<正>Alzheimer’s disease (AD) is a devastating neurodegenerative disease and the most common form of dementia in the elderly. Concurrent with an aging population, the incidence of AD has been rising steadily and become a global threat to public health [1]. Unfortunately, there are currently no effective interventions that can cure AD or slow its progression, and recently finished clinical trials targeting     

Combination of Aβ clearance and neurotrophic factors as a potential treatment for Alzheimer’s disease

There is no effective drug to treat Alzheimer’s disease (AD), a neurodegenerative disease affecting an estimated 30 million people around the world. Strongly supported by preclinical and clinical studies, amyloid-beta (Aβ) may be a target for developing drugs against AD. Meanwhile, the fact that localized neuronal death/loss and synaptic impairment occur in AD should also be considered. Neuronal regeneration, which does not occur normally in the mammalian central nervous system, can be promoted by neurotrophic factors (NTFs). Evidence from clinical trials has shown that both Aβ clearance and NTFs are potentially effective in treating AD, thus a new approach combining Aβ clearance and administration of NTFs may be an effective therapeutic strategy.     

Plasma Replacement Therapy for Alzheimer's Disease

正Alzheimer's disease (AD) is the most common neurodegenerative disease that affects memory,thinking,behavior,and the ability to perform everyday activities.It has been estimated that more than 35 million people worldwide suffered from AD in 2018 [1],and this figure continues to grow.Unfortunately,no cure or treatment that slows the progression of the disease has been discovered despite extensive efforts from academics and the pharmaceutical     

Probing the endoplasmic reticulummitochondria interaction in Alzheimer's disease:searching far and wide

<正>Alzheimer’s disease(AD) is the most frequent,form of dementia in elderly people and is an incurable disease with an exponentially growing number of cases.Extracellular deposition of amyloid-β(Aβ)plaques and intraneuronal formation of neurofibrillary tangles represent neuropathological hallmarks of AD.     

The plasminogen activating system in the pathogenesis of Alzheimer’s disease

Dementia is a clinical syndrome that affects approximately 47 million people worldwide and is characterized by progressive and irreversible decline of cognitive,behavioral and sesorimotor functions.Alzheimer’s disease(AD)accounts for approximately 60–80%of all cases of dementia,and neuropathologically is characterized by extracellular deposits of insoluble amyloid-β(Aβ)and intracellular aggregates of hyperphosphorylated tau.Significantly,although for a long time it was believed that the extracellular accumulation of Aβwas the culprit of the symptoms observed in these patients,more recent studies have shown that cognitive decline in people suffering this disease is associated with soluble Aβ-induced synaptic dysfunction instead of the formation of insoluble Aβ-containing extracellular plaques.These observations are translationally relevant because soluble Aβ-induced synaptic dysfunction is an early event in AD that precedes neuronal death,and thus is amenable to therapeutic interventions to prevent cognitive decline before the progression to irreversible brain damage.The plasminogen activating(PA)system is an enzymatic cascade that triggers the degradation of fibrin by catalyzing the conversion of plasminogen into plasmin via two serine proteinases:tissue-type plasminogen activator(tPA)and urokinase-type plasminogen activator(uPA).Experimental evidence reported over the last three decades has shown that tPA and uPA play a role in the pathogenesis of AD.However,these studies have focused on the ability of these plasminogen activators to trigger plasmin-induced cleavage of insoluble Aβ-containing extracellular plaques.In contrast,recent evidence indicates that activity-dependent release of uPA from the presynaptic terminal of cerebral cortical neurons protects the synapse from the deleterious effects of soluble Aβvia a mechanism that does not require plasmin generation or the cleavage of Aβfibrils.Below we discuss the role of the PA system in the pathogenesis of AD and the translational relevance of data published to this date.     

A crate of Pandora:do amyloids from bacteria promote Alzheimer's disease?

正Incidence for microbes as drivers of Alzheimer’s disease (AD) pathology:AD is the predominant neurodegenerative disease within the elderly. Over 50 million patients suffer from dementia currently world-wide and an estimated tripling of numbers within the next 30 years is expected. Only one to maximally five percent of all cases of AD are based on mutations in the amyloid precursor protein (APP) gene or within the presenilin genes (PS1/PS2) and therefore are called familial (FAD).     

Extracellular vesicles drive tau spreading in Alzheimer's disease

Alzheimer's disease(AD) is a progressive and irreversible neurodegenerative disorder that is characterized by memory loss and a decline in activities of daily life. More than 50 million people worldwide are affected by AD, and this number will continue to rise over 100 million within next three decades. Its major pathological features are the extracellular plaque deposits of the β-amyloid peptide and the intracellular flame-shaped neurofibrillary tangle-aggregation of hyperphosphorylated tau-proteins(pTau).     

To treat or not to treat Alzheimer’s disease by the ketogenic diet? That is the question

Alzheimer’s disease (AD) and current treatments: AD is a serious neurological disorder worldwide that affects about 26 million people,and whose prevalence has been calculated to quadruple by 2050,thus reaching over 1% of the total population,with the highest prevalence occurring in both adults and elderly (Pluta et al.,2018).Neurodegenerative processes of the sporadic form of AD probably start 20 years before the clinical onset of the disorder (Pluta et al.,2018).This disease is the most important cause of dementia in world aged society (~75%).AD is a disorder that affects not only patients but also their caregivers.The social and economic burden associated with AD was calculated as an example in the United States alone;600 billion dollars annually is spent on caring for AD patients (Pluta et al.,2018).AD is the one of the great health-care challenges of the 21st century.The incidence of AD,a chronic and progressive neurodegenerative disorder,is increasing,as well as the need for efficient methods of diagnosis,prevention and treatment (Pluta et al.,2018).The characteristic clinical and neuropathological hallmarks of AD are: dementia as the main clinical symptom and in post-mortem neuropathological examination,the presence of amyloid plaques as well as neurofibrillary tangles and loss of neurons in the brain of AD patients.The role of amyloid and tau protein is questioned in the etiology of AD and other causes such as ischemic etiology are being considered (Pluta and U?amek-Kozio?,2019).There are several treatments that are not causal but symptomatic that are not effective,especially for advanced disease.To date,only a few drugs are approved,such as acetylcholinesterase inhibitors and memantine.Drugs that regulate partly the activity of neurotransmitters and partly alleviate behavioral symptoms.Other treatment options include active and passive immunization,anti-aggregation specifics,and secretase inhibitors.The road to clarity AD etiology,early final ante mortem diagnosis and treatment has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution.Research has recently been launched to identify new mechanisms underlying AD that could be the target of new prevention strategies (Pluta and U?amek-Kozio?,2019).Therefore,other treatment options can be recommended,and the ketogenic diet seems to be an interesting last resort solution at the moment (Rusek et al.,2019).The diet contains large amounts of fat and low carbohydrates with vitamin supplementation.New scientific articles suggest that a low-carbohydrate and high-fat ketogenic diet may help alleviate the brain damage in AD (Ota et al.,2019;Rusek et al.,2019).A ketogenic diet can alleviate the effects of impaired glucose metabolism in AD by providing ketones as an additional source of energy.Here,based on new data,we have presented that a ketogenic diet can be effective in preventing and treating AD,but both ketone bodies production and carbohydrate reduction are needed to achieve this.