Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Fišar, Zdeněk

doi:10.3390/biom12111676

Cited by 34 publications

(29 citation statements)

References 420 publications

(491 reference statements)

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“…Moreover, all of them may affect the structure of β-amyloid, thus significantly reducing its concentration in both the cerebral cortex and the hippocampus [ 222 ]. In addition to affecting inflammatory cells and the level of β-amyloid by changing its spatial conformation, NSAIDs modulate the processing of the amyloid precursor protein, impairing the synthesis of β-amyloid at an early stage, primarily affecting the form of Aβ-42, which is considered to be the most responsible for the formation of plaques [ 223 ]. Some NSAIDs, including ibuprofen, may interfere with the activity of enzymes, including γ-secretase and α1-antichymotrypsin, resulting in no abnormalities in APP folding and a lack of toxic oligomers responsible for plaque formation [ 220 ].…”

Section: Treatment Of Inflammation In Admentioning

confidence: 99%

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Twarowski

Herbet

2023

IJMS

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Alzheimer’s disease is one of the most commonly diagnosed cases of senile dementia in the world. It is an incurable process, most often leading to death. This disease is multifactorial, and one factor of this is inflammation. Numerous mediators secreted by inflammatory cells can cause neuronal degeneration. Neuritis may coexist with other mechanisms of Alzheimer’s disease, contributing to disease progression, and may also directly underlie AD. Although much has been established about the inflammatory processes in the pathogenesis of AD, many aspects remain unexplained. The work is devoted in particular to the pathomechanism of inflammation and its role in diagnosis and treatment. An in-depth and detailed understanding of the pathomechanism of neuroinflammation in Alzheimer’s disease may help in the development of diagnostic methods for early diagnosis and may contribute to the development of new therapeutic strategies for the disease.

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Section: Treatment Of Inflammation In Admentioning

confidence: 99%

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Twarowski

Herbet

2023

IJMS

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“…The accumulation of Aβ may also inhibit the mitochondrial peptidasome (PreP), impacting the processing of mitochondrially targeted protein presequences and leading to multiple functional mitochondrial anomalies [ 79 ]. In addition, soluble Aβ oligomers can impair mitochondrial functions, possibly due to interactions with various mitochondrial proteins, including adenine nucleotide translocase, components of the translocase of the outer membrane (TOM) as well as inner membrane (TIM), and cyclophilin D [ 80 ]. Aβ oligomers may also create membrane-spanning channels (amyloid pores), contributing to toxic effects on mitochondria [ 81 ].…”

Section: Oxidative Stress and Alzheimer’s Diseasementioning

confidence: 99%

Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer’s Disease Pathology and Diagnosis

Bir,

Ghosh,

Chauhan

et al. 2024

Antioxidants

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Oxidative burden plays a central role in Alzheimer’s disease (AD) pathology, fostering protein aggregation, inflammation, mitochondrial impairment, and cellular dysfunction that collectively lead to neuronal injury. The role of exosomes in propagating the pathology of neurodegenerative diseases including AD is now well established. However, recent studies have also shown that exosomes are crucial responders to oxidative stress in different tissues. Thus, this offers new insights and mechanistic links within the complex pathogenesis of AD through the involvement of oxidative stress and exosomes. Several studies have indicated that exosomes, acting as intracellular communicators, disseminate oxidatively modified contents from one cell to another, propagating the pathology of AD. Another emerging aspect is the exosome-mediated inhibition of ferroptosis in multiple tissues under different conditions which may have a role in neurodegenerative diseases as well. Apart from their involvement in the pathogenesis of AD, exosomes enter the bloodstream serving as novel noninvasive biomarkers for AD; some of the exosome contents also reflect the cerebral oxidative stress in this disease condition. This review highlights the intricate interplay between oxidative stress and exosome dynamics and underscores the potential of exosomes as a novel tool in AD diagnosis.

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“…Tau proteins in PHFs have more negative charge than tau monomers and are therefore unable to bind to negatively charged tubules or effectively stabilize microtubules. Without tau’s stability, the network of microtubule structures easily disintegrates, causing neurons to no longer function properly ( Ittner et al, 2016 ; Fišar, 2022 ; Denechaud et al, 2023 ).…”

Section: Alzheimer’s Disease-related Tau Pathological Changesmentioning

confidence: 99%

Biomarkers associated with the pathogenesis of Alzheimer’s disease

Wang,

Sun,

et al. 2023

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is a progressive degenerative neurological illness with insidious onset. Due to the complexity of the pathogenesis of AD and different pathological changes, the clinical phenotypes of dementia are diverse, and these pathological changes also interact with each other. Therefore, it is of great significance to search for biomarkers that can diagnose these pathological changes to improve the ability to monitor the course of disease and treat the disease. The pathological mechanism hypothesis with high recognition of AD mainly includes the accumulation of β-amyloid (Aβ) around neurons and hyperphosphorylation of tau protein, which results in the development of neuronal fiber tangles (NFTs) and mitochondrial dysfunction. AD is an irreversible disease; currently, there is no clinical cure or delay in the disease process of drugs, and there is a lack of effective early clinical diagnosis methods. AD patients, often in the dementia stages and moderate cognitive impairment, will seek medical treatment. Biomarkers can help diagnose the presence or absence of specific diseases and their pathological processes, so early screening and diagnosis are crucial for the prevention and therapy of AD in clinical practice. β-amyloid deposition (A), tau pathology (T), and neurodegeneration/neuronal damage (N), also known as the AT (N) biomarkers system, are widely validated core humoral markers for the diagnosis of AD. In this paper, the pathogenesis of AD related to AT (N) and the current research status of cerebrospinal fluid (CSF) and blood related biomarkers were reviewed. At the same time, the limitations of humoral markers in the diagnosis of AD were also discussed, and the future development of humoral markers for AD was prospected. In addition, the contents related to mitochondrial dysfunction, prion virology and intestinal microbiome related to AD are also described, so as to understand the pathogenesis of AD in many aspects and dimensions, so as to evaluate the pathological changes related to AD more comprehensively and accurately.

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Linking the Amyloid, Tau, and Mitochondrial Hypotheses of Alzheimer’s Disease and Identifying Promising Drug Targets

Cited by 34 publications

References 420 publications

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Inflammatory Processes in Alzheimer’s Disease—Pathomechanism, Diagnosis and Treatment: A Review

Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer’s Disease Pathology and Diagnosis

Biomarkers associated with the pathogenesis of Alzheimer’s disease

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