Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system... more
Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism
regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role
in normal central nervous system development andphysiological function. By binding to nuclear
receptors and modulating gene expression, THs influence neuronal migration, differentiation,
myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs
supply deficiency in early life may result inirreversible neurological and motor deficits.The
development and function of GABAergic neurons as well as glutamatergic transmission are also
affected by THs. Though the underlying molecular mechanisms still remainunknown, the effects of
THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring
predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder
known as epilepsy. Pathologically, epilepsy may be accompanied bymitochondrial dysfunction,
oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic
neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we
hypothesizes that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review
gender differences and the presumed underlying mechanisms through which TH abnormalities may
affect epilepsyhere.
regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role
in normal central nervous system development andphysiological function. By binding to nuclear
receptors and modulating gene expression, THs influence neuronal migration, differentiation,
myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs
supply deficiency in early life may result inirreversible neurological and motor deficits.The
development and function of GABAergic neurons as well as glutamatergic transmission are also
affected by THs. Though the underlying molecular mechanisms still remainunknown, the effects of
THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring
predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder
known as epilepsy. Pathologically, epilepsy may be accompanied bymitochondrial dysfunction,
oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic
neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we
hypothesizes that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review
gender differences and the presumed underlying mechanisms through which TH abnormalities may
affect epilepsyhere.
Research Interests:
Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several... more
Glycogen synthase kinase 3 (GSK-3) dysregulation plays an important role in the pathogenesis of numerous disorders, affecting the central nervous system (CNS) encompassing both neuroinflammation and neurodegenerative diseases. Several lines of evidence have illustrated a key role of the GSK-3 and its cellular and molecular signaling cascades in the control of neuroinflammation. Glycogen synthase kinase 3 beta (GSK-3ß), one of the GSK-3 isomers, plays a major role in neuronal apoptosis and its inhibition decreases expression of alphaSynuclein (a-Synuclein), which make this kinase an attractive therapeutic target for neurodegenerative disorders.
Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3ß in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3ß has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3ß inhibitors as therapeutics.
In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3ß and several cellular processes involved in the pathogenesis of PD, including the accumulation of a-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3ß inhibitors as a potential therapeutic strategy in PD.
Parkinson's disease (PD) is a chronic neurodegenerative movement disorder characterized by the progressive and massive loss of dopaminergic neurons by neuronal apoptosis in the substantia nigra pars compacta and depletion of dopamine in the striatum, which lead to pathological and clinical abnormalities. Thus, understanding the role of GSK-3ß in PD will enhance our knowledge of the basic mechanisms underlying the pathogenesis of this disorder and facilitate the identification of new therapeutic avenues. In recent years, GSK-3ß has been shown to play essential roles in modulating a variety of cellular functions, which have prompted efforts to develop GSK-3ß inhibitors as therapeutics.
In this review, we summarize GSK-3 signaling pathways and its association with neuroinflammation. Moreover, we highlight the interaction between GSK-3ß and several cellular processes involved in the pathogenesis of PD, including the accumulation of a-Synuclein aggregates, oxidative stress and mitochondrial dysfunction. Finally, we discuss about GSK-3ß inhibitors as a potential therapeutic strategy in PD.