The Broad Range of Research in Alzheimer's Disease and Related Dementias

DeKosky, Steven T.; Duara, Ranjan

doi:10.1007/s13311-022-01245-4

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…Additional risk factors include having one or more apolipoprotein gene E4 alleles (APOE4), having a family history of AD, having inadequate occupational and educational skills, having cardiovascular risk factors, and having experienced moderate to severe brain injuries [ 57 ]. According to the cholinergic hypothesis, the gradual loss of limbic and neocortical cholinergic innervation in AD is responsible for the decrease in memory, learning, attention, and other higher brain processes [ 58 ]. Furthermore, neurofibrillary degeneration in the basal forebrain is most likely the major source of cholinergic cell malfunction and mortality in this area, resulting in broad presynaptic cholinergic denervation.…”

Section: Alzheimer’s Diseasementioning

confidence: 99%

Bioactive Compounds of the Mediterranean Diet as Nutritional Support to Fight Neurodegenerative Disease

Franco

Interdonato

Cordaro

et al. 2023

IJMS

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Neurodegenerative disorders are a widespread cause of morbidity and mortality worldwide, characterized by neuroinflammation, oxidative stress, and neuronal depletion. They include selective malfunction and progressive loss of neurons, glial cells, and neural networks in the brain and spinal cord. There is an urgent need to develop new and more effective therapeutic strategies to combat these devastating diseases because, today, there is no treatment that can cure degenerative diseases; however, we have many symptomatic treatments. Current nutritional approaches are beginning to reflect a fundamental change in our understanding of health. The Mediterranean diet may have a protective effect on the neurodegenerative process because it is rich in antioxidants, fiber, and omega-3 polyunsaturated fatty acids. Increasing knowledge regarding the impact of diet on regulation at the genetic and molecular levels is changing the way we consider the role of nutrition, resulting in new dietary strategies. Natural products, thanks to their bioactive compounds, have recently undergone extensive exploration and study for their therapeutic potential for a variety of diseases. Targeting simultaneous multiple mechanisms of action and a neuroprotection approach with the diet could prevent cell death and restore function to damaged neurons. For these reasons, this review will be focused on the therapeutic potential of natural products and the associations between the Mediterranean-style diet (MD), neurodegenerative diseases, and markers and mechanisms of neurodegeneration.

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Section: Alzheimer’s Diseasementioning

confidence: 99%

Bioactive Compounds of the Mediterranean Diet as Nutritional Support to Fight Neurodegenerative Disease

Franco

Interdonato

Cordaro

et al. 2023

IJMS

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show abstract

“…1−5 Alzheimer's disease (AD) and Parkinsonian syndromes are the most representative neurodegenerative disorders that are broadly spreading over the world. 6 Cortical basal degeneration (CBD) and primary supranuclear palsy (PSP) represent atypical forms of Parkinsonian syndromes and are considered as primary tauopathies with an underlying brain aggregation of tau proteins. 7,8 It has been reported that most of these abnormal protein aggregates are present in the brain much in advance of the appearance of dementia symptoms.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Proteinopathies is a broad umbrella term used to represent neurodegenerative disorders that are characterized by different target proteins and featured by the formation of abnormal protein aggregates in the brain, such as amyloid-β (Aβ), tau, and α-synuclein. − Alzheimer’s disease (AD) and Parkinsonian syndromes are the most representative neurodegenerative disorders that are broadly spreading over the world . Cortical basal degeneration (CBD) and primary supranuclear palsy (PSP) represent atypical forms of Parkinsonian syndromes and are considered as primary tauopathies with an underlying brain aggregation of tau proteins. , It has been reported that most of these abnormal protein aggregates are present in the brain much in advance of the appearance of dementia symptoms .…”

Section: Introductionmentioning

confidence: 99%

Insight into the Binding of First- and Second-Generation PET Tracers to 4R and 3R/4R Tau Protofibrils

Li,

Kumar,

Långström

et al. 2023

ACS Chem. Neurosci.

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Primary supranuclear palsy (PSP) is a rare neurodegenerative disease that perturbs body movement, eye movement, and walking balance. Similar to Alzheimer's disease (AD), the abnormal aggregation of tau fibrils in the central neuronal and glial cells is a major hallmark of PSP disease. In this study, we use multiple approaches, including docking, molecular dynamics, and metadynamics simulations, to investigate the binding mechanism of 10 first-and second-generations of PET tracers for PSP tau and compare their binding in cortical basal degeneration (CBD) and AD tauopathies. Structure−activity relationships, binding preferences, the nature of ligand binding in terms of basic intermolecular interactions, the role of polar/charged residues, induced-fit mechanisms, grove closures, and folding patterns for the binding of these tracers in PSP, CBD, and AD tau fibrils are evaluated and discussed in detail in order to build a holistic picture of what is essential for the binding and also to rank the potency of the different tracers. For example, we found that the same tracer shows different binding preferences for the surface sites of tau fibrils that are intrinsically distinct in the folding patterns. Results from the metadynamics simulations predict that PMPBB3 and PBB3 exhibit the strongest binding free energies onto the Q 276 [I 277 ]I 278 , Q 351 [S 352 ]K 353 , and N 368 [K 369 ]K 370 sites of PSP than the other explored tracers, indicating a solid preference for vdW and cation−π interactions. Our results also reproduced known preferences of tracers, namely, that MK6240 binds better to AD tau than CBD tau and PSP tau and that CBD2115, PI2620, and PMPBB3 are 4R tau binders. These findings fill in the well-sought-after knowledge gap in terms of these tracers' potential binding mechanisms and will be important for the design of highly selective novel PET tracers for tauopathies.

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Biofilm-camouflaged Prussian blue synergistic mitochondrial mass enhancement for Alzheimer's disease based on Cu2+ chelation and photothermal therapy

Li,

Xiong,

Zhang

et al. 2024

Journal of Controlled Release

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The Broad Range of Research in Alzheimer's Disease and Related Dementias

Abstract: Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Cited by 3 publications

References 27 publications

Bioactive Compounds of the Mediterranean Diet as Nutritional Support to Fight Neurodegenerative Disease

Bioactive Compounds of the Mediterranean Diet as Nutritional Support to Fight Neurodegenerative Disease

Insight into the Binding of First- and Second-Generation PET Tracers to 4R and 3R/4R Tau Protofibrils

Biofilm-camouflaged Prussian blue synergistic mitochondrial mass enhancement for Alzheimer's disease based on Cu2+ chelation and photothermal therapy

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