Roles of PPAR transcription factors in the energetic metabolic switch occurring during adult neurogenesis

Abstract

PPARs are a class of ligand-activated transcription factors belonging to the superfamily of receptors for steroid and thyroid hormones, retinoids and vitamin D that control the expression of a large number of genes involved in lipid and carbohydrate metabolism and in the regulation of cell proliferation, differentiation and death. The role of PPARs in the CNS has been primarily associated with lipid and glucose metabolism; however, these receptors are also implicated in neural cell differentiation and death, as well as neuronal maturation. Although it has been demonstrated that PPARs play important roles in determining NSCs fate, less is known about their function in regulating NSCs metabolism during differentiation. In order to identify the metabolic events, controlled by PPARs, occurring during neuronal precursor differentiation, the glucose and lipid metabolism was followed in a recognized model of neuronal differentiation in vitro, the SH-SY5Y neuroblastoma cell line. Moreover, PPARs distribution were also followed in situ in adult mouse brains. The concept of adult neurogenesis becomes relevant especially in view of those disorders in which a loss of neurons is described, such as Alzheimer disease, Parkinson disease, brain injuries and other neurological disorders. Elucidating the crucial steps in energetic metabolism and the involvement of PPARg in NSC neuronal fate (lineage) may be useful for the future design of preventive and/or therapeutic interventions.

Downregulation of DEC1 contributes to the neurotoxicity induced by MPP+ by suppressing PI3K/Akt/GSK3β pathway

“…Parkinson disease is the second most common neurodegenerative disorder and pathologically characterized by selective loss of dopaminergic neurons in SNpc of the midbrain. The underlying precise mechanisms remain unclear, but the transcriptional factors are recognized to be important contributing factors in the neuron metabolism and maintenance of normal intracellular homeostasis . The bHLH proteins, a superfamily of transcription factors, play an important role in the development and regeneration of the nervous system .…”

“…*P<.05, **P<.01, ***P<.001 vs. control (PBS), # P<.05, ### P<.001 vs. MPP + treatment mechanisms remain unclear, but the transcriptional factors are recognized to be important contributing factors in the neuron metabolism and maintenance of normal intracellular homeostasis. [43][44][45] The bHLH proteins, a superfamily of transcription factors, play an important role in the development and regeneration of the nervous system. 46 Many of bHLH proteins have been implicated in the differentiation and maintenance of mesencephalic dopaminergic neurons.…”

The Novel Role of PPAR Alpha in the Brain: Promising Target in Therapy of Alzheimer’s Disease and Other Neurodegenerative Disorders

“…About 40% of PD patients are affected with cognitive impairment and dementia, which are about 6 times more frequent in PD patient comparing to healthy, age related control people. Several previous studies indicated promising effects of PPAR agonists in PD [95][96][97][98]. Previously also Carta et al [99] reported ameliorating effect of rosiglitazone which decreased PPAR-γ level and inhibited TNFα production in progressive PD mice model.…”

Oleoylethanolamide restores alcohol-induced inhibition of neuronal proliferation and microglial activity in striatum

“…In contrast, a recent study from our group highlighted that the selective CB2 receptor agonist JWH133 specifically counteracted the chronic ethanol exposure-induced impairment of NSPC proliferation and maturation in the main neurogenic niches of the adult rat brain (Rivera et al, 2015b). PPAR isoforms can directly regulate neuronal cell proliferation, survival and differentiation (Cimini and Ceru, 2008;Di Giacomo et al, 2017). Specifically, PPARα can be implicated in the progressive age-associated decline of NSPC proliferation (2, 6 and 18 months), an effect that was partially compensated in enriched environments when PPARα is lacking (Pérez-Martín et al, 2016).…”