Pharmacological approaches to mitigate neuroinflammation in Alzheimer’s disease

Uddin, Sahab; Kabir, Tanvir; Mamun, Abdullah Al; Barreto, George E.; Rashid, Mamunur; Perveen, Asma; Ashraf, Ghulam Md

doi:10.1016/j.intimp.2020.106479

Cited by 86 publications

(42 citation statements)

References 201 publications

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“…44 The pathogenesis of AD is complicated, and it is widely accepted that neurodegeneration can be triggered by a series of interactions including inflammation, oxidative stress, and apoptotic cell death. [45][46][47] In the present study, due to their antioxidant, anti-inflammatory, and neuroprotective properties, quercetin, kaempferol, and beta-sitosterol may be key compounds for YZQX. In addition, a PPI network of YZQX against AD was screened with 110 nodes and 2269 edges, thus highlighting a potential role in AD.…”

Section: Discussionmentioning

confidence: 84%

<p>Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer’s Disease: Coupling Network Pharmacology with GEO Database</p>

Zhang

Pan

Cao

et al. 2020

PGPM

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Background: Yizhiqingxin formula (YZQX) is a promising formula for the treatment of Alzheimer's disease (AD) with significant clinical effects. Here, we coupled a network pharmacology approach with the Gene Expression Omnibus (GEO) database to illustrate comprehensive mechanisms and screen for molecular targets of YZQX for AD treatment. Methods: First, active ingredients of YZQX were screened for the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database with the absorption, distribution, metabolism, and excretion (ADME) parameters. Subsequently, putative targets of active ingredients were predicted using the DrugBank database. AD-related targets were retrieved by analyzing published microarray data (accession number GSE5281). Protein-protein interaction (PPI) networks of YZQX putative targets and AD-related targets were constructed visually and merged to identify candidate targets for YZQX against AD using Cytoscape 3.7.2 software. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to further clarify the biological functions of the candidate targets. The gene-pathway network was established to filter for key target genes. Results: Forty-three active ingredients were identified, and 193 putative target genes were predicted. Seven hundred and ten targets related to AD were screened with |log2 FC| > 1 and P < 0.05. Based on the PPI network, 110 target genes of YZQX against AD were identified. Moreover, 32 related pathways including the PI3K-Akt signaling pathway, MAPK signaling pathway, ubiquitin-mediated proteolysis, apoptosis and the NF-kappa B signaling pathway were significantly enriched. In the gene-pathway network, MAPK1, AKT1, TP53, MDM2, EGFR, RELA, SRC, GRB2, CUL1, and MYC targets are putative core genes for YZQX in AD treatment. Conclusion: YZQX against AD may exert its neuroprotective effect via the PI3K-Akt signaling pathway, MAPK signaling pathway, and ubiquitin-mediated proteolysis. YZQX may be a promising drug that can be used in the treatment of AD.

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Section: Discussionmentioning

confidence: 84%

<p>Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer’s Disease: Coupling Network Pharmacology with GEO Database</p>

Zhang

Pan

Cao

et al. 2020

PGPM

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“…Inflammation has a significant role in the pathology of AD [280]. Accumulation of Aβ and activation of PKR (i.e., a pro-apoptotic kinase) can take place due to the systemic inflammation.…”

Section: Altering the Interplay Of Aβ And Neuroinflammationmentioning

confidence: 99%

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

Uddin

Kabir

Rahman

et al. 2020

IJMS

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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-β (Aβ), a peptide of 40–42 amino acids. The conversion of Aβ into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aβ accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aβ monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aβ and antagonize Aβ aggregation, or raise Aβ clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aβ which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aβ oligomers have exhibited exciting findings. Nevertheless, Aβ oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aβ monomer or Aβ plaques ought to have displayed valuable clinical benefits. In this article, Aβ-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

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“…The release of cytokines also activates COX-2 dependent prostanoid releases. Furthermore, prostaglandins (PGs) also play a pivotal role in triggering inflammation that increases sensitivity to pain (Uddin et al, 2020b). It had been found that intrathecal injection of PGs such as PGE 2 and PGF 2α triggered allodynia in conscious mice (Minami et al, 1992(Minami et al, , 1994, while intrathecal administration of PGD 2 and PGE 2 led to the initiation of hyperalgesia (Uda et al, 1990).…”

Section: Effect Of Flavonoids On Other Neuropathic Pain Signaling Patmentioning

confidence: 99%

Exploring the Promise of Flavonoids to Combat Neuropathic Pain: From Molecular Mechanisms to Therapeutic Implications

et al. 2020

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Neuropathic pain (NP) is the result of irregular processing in the central or peripheral nervous system, which is generally caused by neuronal injury. The management of NP represents a great challenge owing to its heterogeneous profile and the significant undesirable side effects of the frequently prescribed psychoactive agents, including benzodiazepines (BDZ). Currently, several established drugs including antidepressants, anticonvulsants, topical lidocaine, and opioids are used to treat NP, but they exert a wide range of adverse effects. To reduce the burden of adverse effects, we need to investigate alternative therapeutics for the management of NP. Flavonoids are the most common secondary metabolites of plants used in folkloric medicine as tranquilizers, and have been claimed to have a selective affinity to the BDZ binding site. Several studies in animal models have reported that flavonoids can reduce NP. In this paper, we emphasize the potentiality of flavonoids for the management of NP.

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Pharmacological approaches to mitigate neuroinflammation in Alzheimer’s disease

Cited by 86 publications

References 201 publications

<p>Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer’s Disease: Coupling Network Pharmacology with GEO Database</p>

<p>Identifying the Mechanisms and Molecular Targets of Yizhiqingxin Formula on Alzheimer’s Disease: Coupling Network Pharmacology with GEO Database</p>

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

Exploring the Promise of Flavonoids to Combat Neuropathic Pain: From Molecular Mechanisms to Therapeutic Implications

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