New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease

Penke, Botond; Szücs, Mária; Bogár, Ferenc

doi:10.3390/ijms24065383

Cited by 17 publications

(9 citation statements)

References 185 publications

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“…Recently, research concerning dementia has focused on new possible treatments for AD. Amyloid-specific monoclonal antibodies have raised hopes for treatments in the early stages of the disease [40]; nevertheless, drug combinations involving multiple molecular targets should be considered [41]. In that sense, all aspects of AD, including genetic factors, need to be clarified in order to identify possible targets for prevention and treatment.…”

Section: Discussionmentioning

confidence: 99%

Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer’s Disease: Results from the HELIAD Study

Sampatakakis,

Mourtzi,

Charisis

et al. 2024

CIMB

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The present study investigated the association of genetic predisposition for white matter hyperintensities (WMHs) with incident amnestic mild cognitive impairment (aMCI) or Alzheimer’s disease (AD), as well as whether such an association was influenced by age, sex, and cognitive reserve. Overall, 537 individuals without aMCI or dementia at baseline were included. Among them, 62 individuals developed aMCI/AD at follow up. Genetic propensity to WMH was estimated using a polygenic risk score for WMHs (PRS WMH). The association of PRS WMH with aMCI/AD incidence was examined using COX models. A higher PRS WMH was associated with a 47.2% higher aMCI/AD incidence (p = 0.015) in the fully adjusted model. Subgroup analyses showed significant results in the older age group, in which individuals with a higher genetic predisposition for WMHs had a 3.4-fold higher risk for developing aMCI/AD at follow up (p < 0.001), as well as in the lower cognitive reserve (CR, proxied by education years) group, in which individuals with a higher genetic predisposition for WMHs had an over 2-fold higher risk (p = 0.013). Genetic predisposition for WMHs was associated with aMCI/AD incidence, particularly in the group of participants with a low CR. Thus, CR might be a modifier in the relationship between genetic predisposition for WMHs and incident aMCI/AD.

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Section: Discussionmentioning

confidence: 99%

Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer’s Disease: Results from the HELIAD Study

Sampatakakis,

Mourtzi,

Charisis

et al. 2024

CIMB

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“…Mitochondria, mitochondria-associated membranes (MAMs), and endoplasmic reticulum (ER), which are connected to the ubiquitin proteasome system, autophagy system, ROS production, The main pathophysiological feature of AD is impaired proteostasis of pathways involved in the synthesis, folding, post-translational modifications, aggregation, targeting, and degradation of Aβ and tau protein in the brain. Mitochondria, mitochondria-associated membranes (MAMs), and endoplasmic reticulum (ER), which are connected to the ubiquitin proteasome system, autophagy system, ROS production, regulation of free cytosolic calcium, and apoptosis, are significantly involved in these processes [14][15][16][17].…”

Section: Alzheimer's Diseasementioning

confidence: 99%

CoQ10 and Mitochondrial Dysfunction in Alzheimer’s Disease

Fišar,

Hroudová

2024

Antioxidants

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The progress in understanding the pathogenesis and treatment of Alzheimer’s disease (AD) is based on the recognition of the primary causes of the disease, which can be deduced from the knowledge of risk factors and biomarkers measurable in the early stages of the disease. Insights into the risk factors and the time course of biomarker abnormalities point to a role for the connection of amyloid beta (Aβ) pathology, tau pathology, mitochondrial dysfunction, and oxidative stress in the onset and development of AD. Coenzyme Q10 (CoQ10) is a lipid antioxidant and electron transporter in the mitochondrial electron transport system. The availability and activity of CoQ10 is crucial for proper mitochondrial function and cellular bioenergetics. Based on the mitochondrial hypothesis of AD and the hypothesis of oxidative stress, the regulation of the efficiency of the oxidative phosphorylation system by means of CoQ10 can be considered promising in restoring the mitochondrial function impaired in AD, or in preventing the onset of mitochondrial dysfunction and the development of amyloid and tau pathology in AD. This review summarizes the knowledge on the pathophysiology of AD, in which CoQ10 may play a significant role, with the aim of evaluating the perspective of the pharmacotherapy of AD with CoQ10 and its analogues.

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“… 63 , 64 Some new therapies involving the modulation of microglia phagocytosis have been suggested. 65 …”

Section: Immunology Of Ndgmentioning

confidence: 99%

Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants

Houldsworth

2023

Brain Communications

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Neurological disorders include a variety of conditions, Alzheimer’s disease, Motor Neuron disease, and Parkinson’s disease, affecting longevity and quality of life and their pathogenesis is associated with oxidative stress. Several of the chronic neurodegenerative pathologies of the central nervous system share some common features, such as, oxidative stress, inflammation, synapse dysfunctions, protein misfolding, and defective autophagia. Neuroinflammation can involve the activation of mast cells, contributing to oxidative stress, in addition other the sources of reactive oxygen species. Antioxidants can powerfully neutralise reactive oxygen species and free radicals, decreasing oxidative damage. Antioxidant genes, like manganese superoxide dismutase enzyme, can undergo epigenetic changes that reduce their expression, thus increasing oxidative stress in tissue. Alternatively, DNA can be altered by free radical damage. The epigenetic landscape of these genes can change antioxidant function and may result in neurodegenerative disease. This imbalance of free radical production and antioxidant function increases the reactive oxygen species that cause cell damage in neurons and is often observed as an age-related event. Increased antioxidant expression in mice is protective against reactive oxygen species in neurons as is the exogenous supplementation of antioxidants. Manganese superoxide dismutase requires manganese for its enzymic function. Antioxidant therapy is considered for age-related neurodegenerative diseases and new mimetic of a manganese superoxide dismutase, Avasopasem Manganese is described and suggested as putative treatment to reduce the oxidative stress that causes neurodegenerative disease. The aim of this narrative review is to explore the evidence that oxidative stress causes neurodegenerative damage and the role of antioxidant genes in inhibiting reactive oxygen species damage. Can the neuronal environment of oxidative stress, causing neuroinflammation and neurodegeneration, be reduced or reversed?

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New Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease

Cited by 17 publications

References 185 publications

Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer’s Disease: Results from the HELIAD Study

Genetic Predisposition for White Matter Hyperintensities and Risk of Mild Cognitive Impairment and Alzheimer’s Disease: Results from the HELIAD Study

CoQ10 and Mitochondrial Dysfunction in Alzheimer’s Disease

Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants

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