scholarly journals Flotillin: A Promising Biomarker for Alzheimer’s Disease

2020 ◽  
Vol 10 (2) ◽  
pp. 20 ◽  
Author(s):  
Efthalia Angelopoulou ◽  
Yam Nath Paudel ◽  
Mohd. Farooq Shaikh ◽  
Christina Piperi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Rafts ◽  
Protein Interactions ◽  
Tau Protein ◽  
Clinical Evidence ◽  
Senile Plaques ◽  
App Processing ◽  
Protein Levels

Alzheimer’s disease (AD) is characterized by the accumulation of beta amyloid (Aβ) in extracellular senile plaques and intracellular neurofibrillary tangles (NFTs) mainly consisting of tau protein. Although the exact etiology of the disease remains elusive, accumulating evidence highlights the key role of lipid rafts, as well as the endocytic pathways in amyloidogenic amyloid precursor protein (APP) processing and AD pathogenesis. The combination of reduced Aβ42 levels and increased phosphorylated tau protein levels in the cerebrospinal fluid (CSF) is the most well established biomarker, along with Pittsburgh compound B and positron emission tomography (PiB-PET) for amyloid imaging. However, their invasive nature, the cost, and their availability often limit their use. In this context, an easily detectable marker for AD diagnosis even at preclinical stages is highly needed. Flotillins, being hydrophobic proteins located in lipid rafts of intra- and extracellular vesicles, are mainly involved in signal transduction and membrane–protein interactions. Accumulating evidence highlights the emerging implication of flotillins in AD pathogenesis, by affecting APP endocytosis and processing, Ca2+ homeostasis, mitochondrial dysfunction, neuronal apoptosis, Aβ-induced neurotoxicity, and prion-like spreading of Aβ. Importantly, there is also clinical evidence supporting their potential use as biomarker candidates for AD, due to reduced serum and CSF levels that correlate with amyloid burden in AD patients compared with controls. This review focuses on the emerging preclinical and clinical evidence on the role of flotillins in AD pathogenesis, further addressing their potential usage as disease biomarkers.

scholarly journals Role of PrPC Expression in Tau Protein Levels and Phosphorylation in Alzheimer’s Disease Evolution

2014 ◽  
Vol 51 (3) ◽  
pp. 1206-1220 ◽  
Author(s):  
C. Vergara ◽  
L. Ordóñez-Gutiérrez ◽  
F. Wandosell ◽  
I. Ferrer ◽  
J. A. del Río ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Disease Evolution ◽  
Protein Levels

scholarly journals Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model

2021 ◽  
Vol 22 (22) ◽  
pp. 12181
Author(s):  
Guido Santos ◽  
Mario Díaz
Keyword(s):  
Alzheimer’S Disease ◽  
Mathematical Model ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Lipid Rafts ◽  
Brain Cortex ◽  
Clinical Symptoms ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Human Brain Cortex

Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant of the disease is age. Lipid rafts are microdomains present in nerve cell membranes and they are known to play a significant role in the generation of hallmark proteinopathies associated to AD, namely senile plaques, formed by aggregates of amyloid β peptides. Recent studies have demonstrated that human brain cortex lipid rafts are altered during early neuropathological phases of AD as defined by Braak and Braak staging. The lipid composition and physical properties of these domains appear altered even before clinical symptoms are detected. Here, we use a coarse grain molecular dynamics mathematical model to predict the dimensional evolution of these domains using the experimental data reported by our group in human frontal cortex. The model predicts significant size and frequency changes which are detectable at the earliest neuropathological stage (ADI/II) of Alzheimer’s disease. Simulations reveal a lower number and a larger size in lipid rafts from ADV/VI, the most advanced stage of AD. Paralleling these changes, the predictions also indicate that non-rafts domains undergo simultaneous alterations in membrane peroxidability, which support a link between oxidative stress and AD progression. These synergistic changes in lipid rafts dimensions and non-rafts peroxidability are likely to become part of a positive feedback loop linked to an irreversible amyloid burden and neuronal death during the evolution of AD neuropathology.

scholarly journals Activate or Inhibit? Implications of Autophagy Modulation as a Therapeutic Strategy for Alzheimer’s Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6739
Author(s):  
Sharmeelavathi Krishnan ◽  
Yasaswi Shrestha ◽  
Dona P. W. Jayatunga ◽  
Sarah Rea ◽  
Ralph Martins ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Therapeutic Strategy ◽  
Senile Plaques ◽  
Physiological State ◽  
Proteotoxic Stress ◽  
Underlying Causes ◽  
The Brain

Neurodegenerative diseases result in a range of conditions depending on the type of proteinopathy, genes affected or the location of the degeneration in the brain. Proteinopathies such as senile plaques and neurofibrillary tangles in the brain are prominent features of Alzheimer’s disease (AD). Autophagy is a highly regulated mechanism of eliminating dysfunctional organelles and proteins, and plays an important role in removing these pathogenic intracellular protein aggregates, not only in AD, but also in other neurodegenerative diseases. Activating autophagy is gaining interest as a potential therapeutic strategy for chronic diseases featuring protein aggregation and misfolding, including AD. Although autophagy activation is a promising intervention, over-activation of autophagy in neurodegenerative diseases that display impaired lysosomal clearance may accelerate pathology, suggesting that the success of any autophagy-based intervention is dependent on lysosomal clearance being functional. Additionally, the effects of autophagy activation may vary significantly depending on the physiological state of the cell, especially during proteotoxic stress and ageing. Growing evidence seems to favour a strategy of enhancing the efficacy of autophagy by preventing or reversing the impairments of the specific processes that are disrupted. Therefore, it is essential to understand the underlying causes of the autophagy defect in different neurodegenerative diseases to explore possible therapeutic approaches. This review will focus on the role of autophagy during stress and ageing, consequences that are linked to its activation and caveats in modulating this pathway as a treatment.

scholarly journals Relationship of Wine Consumption with Alzheimer’s Disease

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 206 ◽  
Author(s):  
Reale ◽  
Costantini ◽  
Jagarlapoodi ◽  
Khan ◽  
Belwal ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Alcohol Intake ◽  
Senile Plaques ◽  
Neuronal Loss ◽  
Language Function ◽  
Reduce Risk ◽  
Relationship Of ◽  
The Relationship

Background: Alzheimer’s disease (AD), the most threatening neurodegenerative disease, is characterized by the loss of memory and language function, an unbalanced perception of space, and other cognitive and physical manifestations. The pathology of AD is characterized by neuronal loss and the extensive distribution of senile plaques and neurofibrillary tangles (NFTs). The role of environment and the diet in AD is being actively studied, and nutrition is one of the main factors playing a prominent role in the prevention of neurodegenerative diseases. In this context, the relationship between dementia and wine use/abuse has received increased research interest, with varying and often conflicting results. Scope and Approach: With this review, we aimed to critically summarize the main relevant studies to clarify the relationship between wine drinking and AD, as well as how frequency and/or amount of drinking may influence the effects. Key Findings and Conclusions: Overall, based on the interpretation of various studies, no definitive results highlight if light to moderate alcohol drinking is detrimental to cognition and dementia, or if alcohol intake could reduce risk of developing AD.

Role of tau protein in Alzheimer's disease: The prime pathological player

2020 ◽  
Vol 163 ◽  
pp. 1599-1617 ◽  
Author(s):  
Shibi Muralidar ◽  
Senthil Visaga Ambi ◽  
Saravanan Sekaran ◽  
Diraviyam Thirumalai ◽  
Balamurugan Palaniappan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein

Protein–protein interactions in the assembly and subcellular trafficking of the BACE (β-site amyloid precursor protein-cleaving enzyme) complex of Alzheimer's disease

2007 ◽  
Vol 35 (5) ◽  
pp. 974-979 ◽  
Author(s):  
R.B. Parsons ◽  
B.M. Austen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Protein Interactions ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid ◽  
Ad Alzheimer’S Disease

The correct assembly of the BACE (β-site amyloid precursor protein-cleaving enzyme or β-secretase) complex and its subsequent trafficking to cellular compartments where it associates with the APP (amyloid precursor protein) is essential for the production of Aβ (amyloid β-peptide), the protein whose aggregation into senile plaques is thought to be responsible for the pathogenesis of AD (Alzheimer's disease). These processes rely upon both transient and permanent BACE–protein interactions. This review will discuss what is currently known about these BACE–protein interactions and how they may reveal novel therapeutic targets for the treatment of AD.

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