Intranasal metformin treatment ameliorates cognitive functions via insulin signaling pathway in ICV-STZ-induced mice model of Alzheimer's disease

Kazkayası, İnci; Telli, Gökçen; Nemutlu, Emirhan; Shanmugasundaram, Uma

doi:10.1016/j.lfs.2022.120538

Cited by 19 publications

(6 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By triggering the mammalian target of rapamycin (mTOR) signaling in elderly ApoE3-target replacement (TR) mice, metformin increased the expression of postsynaptic proteins, thus enhancing cognition (Zhang et al, 2019). Intranasal metformin produced higher metformin concentrations in the hippocampus and lowered plasma concentrations, which enhanced insulin sensitivity more than oral treatment in mice with intracerebroventricular-streptozotocin (ICV-STZ)-induced AD (Kazkayasi et al, 2022). In SH-SY5Y cells and Transgenic mice (Tg6799), metformin exacerbated the pathogenesis of AD by promoting β-APP processing in autophagosomes to boost the production of Aβ (Son et al, 2016).…”

Section: Metforminmentioning

confidence: 99%

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Wang

Liu

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Alzheimer’s Disease (AD) is a global chronic disease in adults with beta-amyloid (Aβ) deposits and hyperphosphorylated tau protein as the pathologic characteristics. Although the exact etiology of AD is still not fully elucidated, aberrant metabolism including insulin signaling and mitochondria dysfunction plays an important role in the development of AD. Binding to insulin receptor substrates, insulin can transport through the blood-brain barrier (BBB), thus mediating insulin signaling pathways to regulate physiological functions. Impaired insulin signaling pathways, including PI3K/Akt/GSK3β and MAPK pathways, could cause damage to the brain in the pathogenesis of AD. Mitochondrial dysfunction and overexpression of TXNIP could also be causative links between AD and DM. Some antidiabetic medicines may have benefits in the treatment of AD. Metformin can be beneficial for cognition improvement in AD patients, although results from clinical trials were inconsistent. Exendin-4 may affect AD in animal models but there is a lack of clinical trials. Liraglutide and dulaglutide could also benefit AD patients in adequate clinical studies but not semaglutide. Dipeptidyl peptidase IV inhibitors (DPP4is) such as saxagliptin, vildagliptin, linagliptin, and sitagliptin could boost cognitive function in animal models. And SGLT2 inhibitors such as empagliflozin and dapagliflozin were also considerably protective against new-onset dementia in T2DM patients. Insulin therapy is a promising therapy but some studies indicated that it may increase the risk of AD. Herbal medicines are helpful for cognitive function and neuroprotection in the brain. For example, polyphenols, alkaloids, glycosides, and flavonoids have protective benefits in cognition function and glucose metabolism. Focusing on glucose metabolism, we summarized the pharmacological mechanism of hypoglycemic drugs and herbal medicines. New treatment approaches including antidiabetic synthesized drugs and herbal medicines would be provided to patients with AD. More clinical trials are needed to produce definite evidence for the effectiveness of hypoglycemic medications.

show abstract

Section: Metforminmentioning

confidence: 99%

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Wang

Liu

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…In the hippocampus and cerebral cortex of intracerebroventricular injection of streptozotocin-induced AD mice, phosphorylation of the insulin receptor, which is the initial reaction that occurs after the receptor is engaged, experienced a notable reduction after intranasal treatment with metformin, according to Kazkayasi et al [118]. The effects of intranasal metformin on pIR and pAkt imply that it restores the damaged insulin signaling pathway by enhancing the insulin sensitivity of neurons in any area of the brain [118].…”

Section: Insulin Signalingmentioning

confidence: 99%

Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders

Isop,

Neculau,

Necula

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer’s, Parkinson’s, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin’s mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as “metformin”, “neuroprotection”, and “neurodegenerative diseases”, with data up to September 2023. Recent research on metformin’s glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1–AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions.

show abstract

“…Vinogradov et al initially introduced the term "NanoGel" in 1999 to describe the particles of a hydrophilic polymer network (PEG-PEI) obtained by crosslinking polyethylene glycol (PEG) (Pappu et al, 2016;Heldt et al, 2019;Kazkayasi et al, 2022) Intrathecal Less invasive Infection, dosedependent drug resistance (Falagas et al, 2007;Jain et al, 2019;Nau et al, 2021;Sari et al, Nanocarriers system Potential toxicity depends on the material used (Bajracharya et al, 2019;de Souza et al, 2020;Wang et al, 2020) and polyethyleneimine (PEI) that were able to deliver antisense oligonucleotides (Zhao et al, 2015). These hydrogel nanoparticles are generally defined as three-dimensional colloidal hydrogel nanoparticles obtained by physical or chemical crosslinking of the polymers with a diameter < 200 nm, thus possessing both the advantages of a hydrogel and characteristics of a nanocarrier system (Goldberg et al, 2007;Zhang et al, 2021a).…”

Section: Properties Of the Nanogelmentioning

confidence: 99%

Nanogels as Novel Nanocarrier Systems for Efficient Delivery of CNS Therapeutics

Zhang

Zou

Liu

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Nanogels have come out as a great potential drug delivery platform due to its prominently high colloidal stability, high drug loading, core-shell structure, good permeation property and can be responsive to environmental stimuli. Such nanoscopic drug carriers have more excellent abilities over conventional nanomaterials for permeating to brain parenchyma in vitro and in vivo. Nanogel-based system can be nanoengineered to bypass physiological barriers via non-invasive treatment, rendering it a most suitable platform for the management of neurological conditions such as neurodegenerative disorders, brain tumors, epilepsy and ischemic stroke, etc. Therapeutics of central nervous system (CNS) diseases have shown marked limited site-specific delivery of CNS by the poor access of various drugs into the brain, due to the presences of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Hence, the availability of therapeutics delivery strategies is considered as one of the most major challenges facing the treatment of CNS diseases. The primary objective of this review is to elaborate the newer advances of nanogel for CNS drugs delivery, discuss the early preclinical success in the field of nanogel technology and highlight different insights on its potential neurotoxicity.

show abstract

Intranasal metformin treatment ameliorates cognitive functions via insulin signaling pathway in ICV-STZ-induced mice model of Alzheimer's disease

Cited by 19 publications

References 61 publications

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Hypoglycemic medicines in the treatment of Alzheimer’s disease: Pathophysiological links between AD and glucose metabolism

Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders

Nanogels as Novel Nanocarrier Systems for Efficient Delivery of CNS Therapeutics

Contact Info

Product

Resources

About