Metformin as a Potential Agent in the Treatment of Multiple Sclerosis

Dziedzic, Angela; Saluk‐Bijak, Joanna; Miller, Elżbieta; Bijak, Michał

doi:10.3390/ijms21175957

Cited by 43 publications

(16 citation statements)

References 171 publications

(180 reference statements)

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“…In several studies performed on mice with traumatic spinal cord injury, reactions of local inflammation along with microglia proliferation, activation, and phagocyte infiltration are used [ 154 ]. In a demyelinating context induced by lysolecithin, metformin treatment reduced demyelination and inflammation and protected the functional integrity of optic tract, as measured by visual evoked potential recording [ 155 ].…”

Section: Molecular Mechanism Involved In Neuroprotective Effects Of Metformin In Alzheimer’s Diseasementioning

confidence: 99%

“…In a demyelinating context induced by lysolecithin, metformin treatment reduced demyelination and inflammation and protected the functional integrity of optic tract, as measured by visual evoked potential recording [ 155 ]. Moreover, potential application of metformin in multiple sclerosis has been recently reviewed [ 154 ].…”

Section: Molecular Mechanism Involved In Neuroprotective Effects Of Metformin In Alzheimer’s Diseasementioning

confidence: 99%

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Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment

et al. 2021

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Alzheimer’s disease (AD) is one of the most devastating brain disorders. Currently, there are no effective treatments to stop the disease progression and it is becoming a major public health concern. Several risk factors are involved in the progression of AD, modifying neuronal circuits and brain cognition, and eventually leading to neuronal death. Among them, obesity and type 2 diabetes mellitus (T2DM) have attracted increasing attention, since brain insulin resistance can contribute to neurodegeneration. Consequently, AD has been referred to “type 3 diabetes” and antidiabetic medications such as intranasal insulin, glitazones, metformin or liraglutide are being tested as possible alternatives. Metformin, a first line antihyperglycemic medication, is a 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activator hypothesized to act as a geroprotective agent. However, studies on its association with age-related cognitive decline have shown controversial results with positive and negative findings. In spite of this, metformin shows positive benefits such as anti-inflammatory effects, accelerated neurogenesis, strengthened memory, and prolonged life expectancy. Moreover, it has been recently demonstrated that metformin enhances synaptophysin, sirtuin-1, AMPK, and brain-derived neuronal factor (BDNF) immunoreactivity, which are essential markers of plasticity. The present review discusses the numerous studies which have explored (1) the neuropathological hallmarks of AD, (2) association of type 2 diabetes with AD, and (3) the potential therapeutic effects of metformin on AD and preclinical models.

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Section: Molecular Mechanism Involved In Neuroprotective Effects Of Metformin In Alzheimer’s Diseasementioning

confidence: 99%

Section: Molecular Mechanism Involved In Neuroprotective Effects Of Metformin In Alzheimer’s Diseasementioning

confidence: 99%

Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment

et al. 2021

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“…Current therapeutic approaches are based on the regulation of autoimmune attacks and the preservation of oligodendrocyte function. Metformin alleviates oxidative stress and restores mitochondrial function in patients with multiple sclerosis [54,55]. Furthermore, in an AMPK-dependent manner, metformin was able to enhance the expression of genes involved in the protection of oligodendrocytes and the restoration of central nervous system functions in an experimental model of autoimmune encephalomyelitis [56].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

Sanz

Serratosa

Sánchez

2021

IJMS

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Metformin is a drug in the family of biguanide compounds that is widely used in the treatment of type 2 diabetes (T2D). Interestingly, the therapeutic potential of metformin expands its prescribed use as an anti-diabetic drug. In this sense, it has been described that metformin administration has beneficial effects on different neurological conditions. In this work, we review the beneficial effects of this drug as a neuroprotective agent in different neurological diseases, with a special focus on epileptic disorders and Lafora disease, a particular type of progressive myoclonus epilepsy. In addition, we review the different proposed mechanisms of action of metformin to understand its function at the neurological level.

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“…Evidence has been mounting for a vascular component in MS, whereby vascular abnormalities play a crucial role in lesion formation and progression (113). The evidence for this notion comes from reports of enhanced risk of cardiovascular events, such as ischemic stroke, myocardial infarction, and thrombosis in MS patients, directly associated with a dysfunctional coagulation cascade and aberrant platelet function and their increased pro-thrombotic activity (54,114).…”

Section: Potential Pathways For Platelet Involvement In Msmentioning

confidence: 99%

Platelets in Multiple Sclerosis: Early and Central Mediators of Inflammation and Neurodegeneration and Attractive Targets for Molecular Imaging and Site-Directed Therapy

et al. 2021

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Platelets are clearly central to thrombosis and hemostasis. In addition, more recently, evidence has emerged for non-hemostatic roles of platelets including inflammatory and immune reactions/responses. Platelets express immunologically relevant ligands and receptors, demonstrate adhesive interactions with endothelial cells, monocytes and neutrophils, and toll-like receptor (TLR) mediated responses. These properties make platelets central to innate and adaptive immunity and potential candidate key mediators of autoimmune disorders. Multiple sclerosis (MS) is the most common chronic autoimmune central nervous system (CNS) disease. An association between platelets and MS was first indicated by the increased adhesion of platelets to endothelial cells. This was followed by reports identifying structural and functional changes of platelets, their chronic activation in the peripheral blood of MS patients, platelet presence in MS lesions and the more recent revelation that these structural and functional abnormalities are associated with all MS forms and stages. Investigations based on the murine experimental autoimmune encephalomyelitis (EAE) MS model first revealed a contribution to EAE pathogenesis by exacerbation of CNS inflammation and an early role for platelets in EAE development via platelet-neuron and platelet-astrocyte associations, through sialated gangliosides in lipid rafts. Our own studies refined and extended these findings by identifying the critical timing of platelet accumulation in pre-clinical EAE and establishing an initiating and central rather than merely exacerbating role for platelets in disease development. Furthermore, we demonstrated platelet-neuron associations in EAE, coincident with behavioral changes, but preceding the earliest detectable autoreactive T cell accumulation. In combination, these findings establish a new paradigm by asserting that platelets play a neurodegenerative as well as a neuroinflammatory role in MS and therefore, that these two pathological processes are causally linked. This review will discuss the implications of these findings for our understanding of MS, for future applications for imaging toward early detection of MS, and for novel strategies for platelet-targeted treatment of MS.

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Metformin as a Potential Agent in the Treatment of Multiple Sclerosis

Cited by 43 publications

References 171 publications

Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment

Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

Platelets in Multiple Sclerosis: Early and Central Mediators of Inflammation and Neurodegeneration and Attractive Targets for Molecular Imaging and Site-Directed Therapy

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