Neuroprotective effects of MHY908, a PPAR α/γ dual agonist, in a MPTP-induced Parkinson’s disease model

Lee, Yujeong; Cho, Jung-Hyun; Lee, Seulah; Lee, Wonjong; Chang, Seung‐Cheol; Chung, Hae Young; Moon, Hyung Ryong; Lee, Jaewon

doi:10.1016/j.brainres.2018.09.036

Cited by 28 publications

(28 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PPAR-α agonist fenofibrate and palmitoylethanolamide could prevent DA cell death in the SNpc, attenuate the loss of TH immunoreactivity in the striatum, and reverse motor deficits by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [56,57] or 6-hydroxydopamine (6-OHDA) [58]. PPAR-α agonist fenofibrate, PPAR-γ agonist pioglitazone, and PPAR-α/γ dual agonist 2-[4-(5-chlorobenzo [d] thiazol-2-yl) phenoxy]-2-methylpropanoic acid (MHY908) could also protect against DA neuronal loss, motor deficit, depression-like behavior, and the impairment of learning and memory caused by MPTP [59][60][61]. PPAR-β/δ is expressed in the nuclei of DA neurons and in astrocytes.…”

Section: Discussionmentioning

confidence: 99%

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

Kao

Wei

Tsai

et al. 2019

IJMS

View full text Add to dashboard Cite

Although several epidemiologic and animal studies have revealed correlations between obesity and neurodegenerative disorders, such as Parkinson disease (PD), the underlying pathological mechanisms of obesity-induced PD remain unclear. Our study aimed to assess the effect of diet-induced obesity on the brain dopaminergic pathway. For five months, starting from weaning, we gave C57BL/6 mice a high-fat diet (HFD) to generate an obese mouse model and investigate whether the diet reprogrammed the midbrain dopaminergic system. Tyrosine hydroxylase staining showed that the HFD resulted in fewer dopaminergic neurons in the substantia nigra (SN), but not the striatum. It also induced neuroinflammation, with increased astrogliosis in the SN and striatum. Dendritic spine density in the SN of HFD-exposed mice decreased, which suggested that prolonged HFD altered dopaminergic neuroplasticity. All three peroxisome proliferator-activated receptor (PPAR) subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area of HFD mice when compared to those in controls. This study showed that a prolonged HFD induced neuroinflammation, suppressed PPAR levels, caused degeneration of midbrain dopaminergic neurons, and resulted in symptoms reminiscent of human PD. To our knowledge, this is the first study documenting the effects of an HFD on PPARs in dopaminergic neurons.

show abstract

Section: Discussionmentioning

confidence: 99%

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

Kao

Wei

Tsai

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…In a chronic model of MPTP, rosiglitazone administration protected from loss of dopaminergic neurons and prevented olfactory and motor alteration [55][56][57]. MHY908, a PPAR-α/γ dual agonist, exerts neuroprotective effects by reducing microglial activation and neuroinflammation, thereby diminishing dopaminergic neuronal damage in a MPTP mouse model of PD [135]. Similarly, the PPAR-γ agonist, MDG548 mediates neuroprotection in LPS-stimulated microglia and, in the MPTP mouse model, by boosting phagocytosis and anti-inflammatory cytokines production (e.g., IL-10) [136].…”

Section: Neurological Disordersmentioning

confidence: 97%

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

Tufano

Pinna

2020

Molecules

View full text Add to dashboard Cite

Recently, peroxisome proliferator-activated receptor (PPAR)-α and γ isoforms have been gaining consistent interest in neuropathology and treatment of neuropsychiatric disorders. Several studies have provided evidence that either the receptor expression or the levels of their endogenously-produced modulators are downregulated in several neurological and psychiatric disorders and in their respective animal models. Remarkably, administration of these endogenous or synthetic ligands improves mood and cognition, suggesting that PPARs may offer a significant pharmacological target to improve several neuropathologies. Furthermore, various neurological and psychiatric disorders reflect sustained levels of systemic inflammation. Hence, the strategy of targeting PPARs for their anti-inflammatory role to improve these disorders is attracting attention. Traditionally, classical antidepressants fail to be effective, specifically in patients with inflammation. Non-steroidal anti-inflammatory drugs exert potent antidepressant effects by acting along with PPARs, thereby strongly substantiating the involvement of these receptors in the mechanisms that lead to development of several neuropathologies. We reviewed running findings in support of a role for PPARs in the treatment of neurological diseases, including Alzheimer’s disease or psychiatric disorders, such as major depression. We discuss the opportunity of targeting PPARs as a future pharmacological approach to decrease neuropsychiatric symptoms at the same time that PPAR ligands resolve neuroinflammatory processes.

show abstract

“…Nowadays, the agonist of PPAR gamma (PPARγ) is promising treatment for neuroinflammation-related condition eg. Alzheimer's disease, Parkinson's disease, and stroke (Govindarajulu et al, 2018 ; Wen et al, 2018 ; Lee et al, 2019 ). It was demonstrated that PPAR attenuated the release of pro-inflammatory cytokines and oxidative stress promotors.…”

Section: Hiv-1 and Glutamate Neurotoxicity—the Role Of Glutamate Recementioning

confidence: 99%

The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

Górska

Eugenín

2020

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Glutamate (Glu) is the most abundant excitatory neurotransmitter in the central nervous system (CNS). HIV-1 and viral proteins compromise glutamate synaptic transmission, resulting in poor cell-to-cell signaling and bystander toxicity. In this study, we identified that myeloid HIV-1-brain reservoirs survive in Glu and glutamine (Gln) as a major source of energy. Thus, we found a link between synaptic compromise, metabolomics of viral reservoirs, and viral persistence. In the current manuscript we will discuss all these interactions and the potential to achieve eradication and cure using this unique metabolic profile.

show abstract

Neuroprotective effects of MHY908, a PPAR α/γ dual agonist, in a MPTP-induced Parkinson’s disease model

Cited by 28 publications

References 51 publications

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

Contact Info

Product

Resources

About