Insulin-degrading enzyme (IDE) as a modulator of microglial phenotypes in the context of Alzheimer’s disease and brain aging

Corraliza-Gomez, Miriam; Bermejo, Teresa; Lilue, Jingtao; Rodriguez-Iglesias, Noelia; Valero, Jorge; Cozar-Castellano, Irene; Arranz, Eduardo; Sanchez, Diego; Ganfornina, Maria Dolores

doi:10.1186/s12974-023-02914-7

Cited by 6 publications

(2 citation statements)

References 89 publications

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“…The insulin-degrading enzyme (IDE), a molecule promoting the degradation of amyloid-β in the brain and improving cognitive impairment in AD patients, modulates microglial activity. Consistently, IDE knockout (IDE-KO) mice show region-specific microgliosis and variations in myelin phagocytosis, which affect cytokine production and stress responses (Corraliza-Gomez et al, 2023 ). These microglia can be either neuroprotective or neurotoxic through their production of reactive oxygen species and cytokines.…”

Section: Involvement In Neurological Disordersmentioning

confidence: 90%

Glial cells in the mammalian olfactory bulb

Zhao,

Hu,

Liu

2024

Front. Cell. Neurosci.

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The mammalian olfactory bulb (OB), an essential part of the olfactory system, plays a critical role in odor detection and neural processing. Historically, research has predominantly focused on the neuronal components of the OB, often overlooking the vital contributions of glial cells. Recent advancements, however, underscore the significant roles that glial cells play within this intricate neural structure. This review discus the diverse functions and dynamics of glial cells in the mammalian OB, mainly focused on astrocytes, microglia, oligodendrocytes, olfactory ensheathing cells, and radial glia cells. Each type of glial contributes uniquely to the OB's functionality, influencing everything from synaptic modulation and neuronal survival to immune defense and axonal guidance. The review features their roles in maintaining neural health, their involvement in neurodegenerative diseases, and their potential in therapeutic applications for neuroregeneration. By providing a comprehensive overview of glial cell types, their mechanisms, and interactions within the OB, this article aims to enhance our understanding of the olfactory system's complexity and the pivotal roles glial cells play in both health and disease.

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Section: Involvement In Neurological Disordersmentioning

confidence: 90%

Glial cells in the mammalian olfactory bulb

Zhao,

Hu,

Liu

2024

Front. Cell. Neurosci.

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“…However, in AD, IDE function may become impaired or overwhelmed as a result of oxidative stress and inflammation. For instance, In AD, chronic inflammation is observed in the brain, and inflammatory molecules can alter IDE expression or activity levels [ 119 ]. Pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), have been shown to suppress IDE expression and activity, leading to reduced Aβ degradation [ 120 , 121 ].…”

Section: Ad’s Pathological Features Related To Aβ Plaquesmentioning

confidence: 99%

The duality of amyloid-β: its role in normal and Alzheimer’s disease states

Azargoonjahromi

2024

Mol Brain

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Alzheimer’s disease (AD) is a degenerative neurological condition that gradually impairs cognitive abilities, disrupts memory retention, and impedes daily functioning by impacting the cells of the brain. A key characteristic of AD is the accumulation of amyloid-beta (Aβ) plaques, which play pivotal roles in disease progression. These plaques initiate a cascade of events including neuroinflammation, synaptic dysfunction, tau pathology, oxidative stress, impaired protein clearance, mitochondrial dysfunction, and disrupted calcium homeostasis. Aβ accumulation is also closely associated with other hallmark features of AD, underscoring its significance. Aβ is generated through cleavage of the amyloid precursor protein (APP) and plays a dual role depending on its processing pathway. The non-amyloidogenic pathway reduces Aβ production and has neuroprotective and anti-inflammatory effects, whereas the amyloidogenic pathway leads to the production of Aβ peptides, including Aβ40 and Aβ42, which contribute to neurodegeneration and toxic effects in AD. Understanding the multifaceted role of Aβ, particularly in AD, is crucial for developing effective therapeutic strategies that target Aβ metabolism, aggregation, and clearance with the aim of mitigating the detrimental consequences of the disease. This review aims to explore the mechanisms and functions of Aβ under normal and abnormal conditions, particularly in AD, by examining both its beneficial and detrimental effects.

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Role of Flavonoids in Mitigating the Pathological Complexities and Treatment Hurdles in Alzheimer's Disease

Chib,

Dutta,

Chalotra

et al. 2024

Phytotherapy Research

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With the passage of time, people step toward old age and become more prone to several diseases associated with the age. One such is Alzheimer's disease (AD) which results into neuronal damage and dementia with the progression of age. The existing therapeutics has been hindered by various enkindles like less eminent between remote populations, affordability issues and toxicity profiles. Moreover, lack of suitable therapeutic option further worsens the quality of life in older population. Developing an efficient therapeutic intervention to cure AD is still a challenge for medical fraternity. Recently, alternative approaches attain the attention of researchers to focus on plant‐based therapy in mitigating AD. In this context, flavonoids gained centrality as a feasible treatment in modifying various neurological deficits. This review mainly focuses on the pathological facets and economic burden of AD. Furthermore, we have explored the possible mechanism of flavonoids with the preclinical and clinical aspects for curing AD. Flavonoids being potential therapeutic, target the pathogenic factors of AD such as oxidative stress, inflammation, metal toxicity, Aβ accumulation, modulate neurotransmission and insulin signaling. In this review, we emphasized on potential neuroprotective effects of flavonoids in AD pathology, with focus on both experimental and clinical findings. While preclinical studies suggest promising therapeutic benefits, clinical data remains limited and inconclusive. Thus, further high‐quality clinical trials are necessary to validate the efficacy of flavonoids in AD. The study aim is to promote the plant‐based therapies and encourage people to add flavonoids to regular diet to avail the beneficial effects in preventive therapy for AD.

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Insulin-degrading enzyme (IDE) as a modulator of microglial phenotypes in the context of Alzheimer’s disease and brain aging

Cited by 6 publications

References 89 publications

Glial cells in the mammalian olfactory bulb

Glial cells in the mammalian olfactory bulb

The duality of amyloid-β: its role in normal and Alzheimer’s disease states

Role of Flavonoids in Mitigating the Pathological Complexities and Treatment Hurdles in Alzheimer's Disease

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