Repurposing Peroxisome Proliferator-Activated Receptor Agonists in Neurological and Psychiatric Disorders

Sagheddu, Claudia; Melis, Miriam; Muntoni, Anna Lisa; Pistis, Marco

doi:10.3390/ph14101025

Cited by 20 publications

(12 citation statements)

References 183 publications

(230 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both these molecules have anti-inflammatory properties [ 139 ]. In addition, one study showed that the decrease in PPARα mRNA levels is concomitant with the increased expression of IL-6 and TNFα [ 146 ]. A functional polymorphism L162V in the PPARα gene was observed in a subgroup of schizophrenic patients [ 147 ].…”

Section: Ppar α Agonists: Possible Therapeutic Targets In Schizophreniamentioning

confidence: 99%

Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway

Vallée

2022

IJMS

View full text Add to dashboard Cite

Schizophrenia is a very complex syndrome involving widespread brain multi-dysconnectivity. Schizophrenia is marked by cognitive, behavioral, and emotional dysregulations. Recent studies suggest that inflammation in the central nervous system (CNS) and immune dysfunction could have a role in the pathogenesis of schizophrenia. This hypothesis is supported by immunogenetic evidence, and a higher incidence rate of autoimmune diseases in patients with schizophrenia. The dysregulation of the WNT/β-catenin pathway is associated with the involvement of neuroinflammation in schizophrenia. Several studies have shown that there is a vicious and positive interplay operating between neuroinflammation and oxidative stress. This interplay is modulated by WNT/β-catenin, which interacts with the NF-kB pathway; inflammatory factors (including IL-6, IL-8, TNF-α); factors of oxidative stress such as glutamate; and dopamine. Neuroinflammation is associated with increased levels of PPARγ. In schizophrenia, the expression of PPAR-γ is increased, whereas the WNT/β-catenin pathway and PPARα are downregulated. This suggests that a metabolic-inflammatory imbalance occurs in this disorder. Thus, this research’s triptych could be a novel therapeutic approach to counteract both neuroinflammation and oxidative stress in schizophrenia.

show abstract

Section: Ppar α Agonists: Possible Therapeutic Targets In Schizophreniamentioning

confidence: 99%

Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway

Vallée

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…It has been suggested that PPAR-α and/or other PPARs could be good targets in therapy strategy for the early-advanced stage of AD [22,23,59]. Preclinical and clinical data demonstrate evidence for repurposing PPAR-targeting drugs for neuro-psychiatric diseases, including AD [59]. This subject was also considered by Nisbett et al [60] and by Tufano and Pinna [61].…”

Section: Discussionmentioning

confidence: 97%

“…Early pharmacological intervention to enhance transcription of Tfam and Nrf2 may maintain mtDNA stability and mitochondrial biogenesis and could be a promising approach to retard the progression of AD. It has been suggested that PPAR-α and/or other PPARs could be good targets in therapy strategy for the early-advanced stage of AD [22,23,59]. Preclinical and clinical data demonstrate evidence for repurposing PPAR-targeting drugs for neuro-psychiatric diseases, including AD [59].…”

Section: Discussionmentioning

confidence: 99%

Changes in transcription of genes encoding NAD-dependent enzymes and mitochondrial proteins in Alzheimer’s disease animal model. Indication of early targets in neuroprotection

Żulińska

Wencel

Wieczorek

et al. 2023

Preprint

View full text Add to dashboard Cite

Oxidative stress and disturbances of mitochondria function in the brain play a crucial role in Alzheimer’s disease (AD). However, little is known about these changes at the early stages of AD. This study aimed to determine the expression of genes encoding superoxide dismutase’s (SOD1, SOD2), Sirtuins (SIRTs) and poly (ADP-ribose) polymerases (PARPs). Moreover, transcription of genes of electron transport complexes (ETC) and proteins of mitochondrial biogenesis in the brain cortex of 3-, 6- and 12-month-old transgenic AD mice was analyzed. Using quantitative qPCR and immunochemical methods, we demonstrated significant decreases in mRNA of Sod2, Sirt1 and Parp1 in the 3-month-old and upregulation of Parp1 in the 6-month-old AD mice. Although levels of mRNA encoding ETC, respiratory complexes subunits (I-II) were negligibly altered, the mRNA mt-CytB and mt-Co1 (complex III, IV) was increased in 12- and 6-month-old AD brains, respectively. These changes were linked to lower cytochrome C oxidase activity in 3- and significantly in 6-month-old AD mice. Several genes involved in mitochondria biogenesis, such as Nrf1, Nrf2 and Tfam, were upregulated in the 3- and 6-month-old AD Tg brain. However, in 12-month-old AD mice, transcription of genes encoding NRF2, PPAR-α, and PGC1-α was significantly downregulated. In summary, our data identified significant changes in gene expression of Sod2, Sirt1 and Parp1 at an early age (3–6 month-old AD mice) and Nrf2, Ppargc1, Ppar-α at the later stage of AD mice. Recognizing these alterations earlier may be important in providing potential therapeutic targets for delaying the progression of pathology in AD.

show abstract

“…Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors activated by small lipophilic molecules. Once activated by their ligand, these receptors bind to DNA sequences and regulate gene expression by transcriptional co-activation [ 351 , 352 ]. More specifically, activated PPARs form a complex in the cytoplasm with the retinoid X receptor-α [ 353 ].…”

Section: Neuroprotective Effect Of Drugs Under Developmentmentioning

confidence: 99%

A Narrative Review on Axonal Neuroprotection in Multiple Sclerosis

et al. 2022

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) resulting in demyelination and neurodegeneration. The therapeutic strategy is now largely based on reducing inflammation with immunosuppressive drugs. Unfortunately, when disease progression is observed, no drug offers neuroprotection apart from its anti-inflammatory effect. In this review, we explore current knowledge on the assessment of neurodegeneration in MS and look at putative targets that might prove useful in protecting the axon from degeneration. Among them, Bruton’s tyrosine kinase inhibitors, anti-apoptotic and antioxidant agents, sex hormones, statins, channel blockers, growth factors, and molecules preventing glutamate excitotoxicity have already been studied. Some of them have reached phase III clinical trials and carry a great message of hope for our patients with MS.

show abstract

Repurposing Peroxisome Proliferator-Activated Receptor Agonists in Neurological and Psychiatric Disorders

Cited by 20 publications

References 183 publications

Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway

Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway

Changes in transcription of genes encoding NAD-dependent enzymes and mitochondrial proteins in Alzheimer’s disease animal model. Indication of early targets in neuroprotection

A Narrative Review on Axonal Neuroprotection in Multiple Sclerosis

Contact Info

Product

Resources

About