Gamma aminobutyric acid (GABA) modulators for amyotrophic lateral sclerosis/motor neuron disease

Abstract

Gamma aminobutyric acid (GABA) modulators for amyotrophic lateral sclerosis/motor neuron disease.

Enhanced motor cortex output and disinhibition in asymptomatic female mice with C9orf72 genetic expansion

“…Interestingly, in mammalian neurons, the SV2a exhibits a high expression specifically at inhibitory synapses, where it plays an important role in sorting of synaptotagmin I (Bae et al, 2020), thus offering a plausible mechanism that can be responsible for early deficit in GABA release in M1 L5-PYRs of c9-500 mice. Selective targeting of vesicle proteins at inhibitory synapses may represent a good alternative to broad pharmacological manipulations with GABA B receptors, which regulate GABA release but were ineffective in ALS clinical trials (Diana et al, 2017).…”

Enhanced motor cortex output and disinhibition in asymptomatic female mice with C9orf72 genetic expansion

“…Interestingly, in mammalian neurons, the SV2a exhibits a high expression specifically at inhibitory synapses, where it plays an important role in sorting of synaptotagmin I (Bae et al, 2020), thus offering a plausible mechanism that can be responsible for early deficit in GABA release in M1 L5-PYRs of c9-500 mice. Selective targeting of vesicle proteins at inhibitory synapses may represent a good alternative to broad pharmacological manipulations with GABA B receptors, which regulate GABA release but were ineffective in ALS clinical trials (Diana et al, 2017).…”

TDP-43 regulates GAD1 mRNA splicing and GABA signaling in Drosophila CNS

“…Interestingly, our results are in line with other evidences obtained from different ALS models, Boussicault et al 2020 demonstrated that GABA agonists treatment synergistically improved the phenotype in primary cultures of motoneurons derived from SOD1 G93A rat embryos 34 . On the other hand, clinical trials using GABA agonists to treat ALS patients have not yet yielded significant results suggesting that the modulation of GABA neurotransmission alone may not be sufficient to overcome the complete symptoms of the disease 35 . More sophisticated therapies, perhaps combining GABAergic with anti-glutamatergic approaches, might be required to re-stablish the neurotransmitter balance in TDP-43 affected brains.…”

Effects of Sub-Acute Manganese Exposure on Thyroid Hormone and Glutamine (Gln)/Glutamate (Glu)-γ- Aminobutyric Acid (GABA) Cycle in Serum of Rats

“…Thus, impairments of the Gln/Glu–GABA cycle in the brain are associated with movement disorders and motor deficits, and they are involved in the genesis and development of neurodegenerative disease, such as idiopathic PD, Huntington’s disease, amyotrophic lateral sclerosis (ALS), etc. [54,55,56,57]. It is well known that injury of dopaminergic neurons is involved in neurotoxicity induced by Mn [4,56].…”

Enhanced motor cortex output and disinhibition in asymptomatic female mice with C9orf72 genetic expansion

“…Interestingly, in mammalian neurons, the SV2a exhibits a high expression specifically at inhibitory synapses, where it plays an important role in sorting of synaptotagmin I (Bae et al, 2020), thus offering a plausible mechanism that can be responsible for early deficit in GABA release in M1 L5-PYRs of c9-500 mice. Selective targeting of vesicle proteins at inhibitory synapses may represent a good alternative to broad pharmacological manipulations with GABA B receptors, which regulate GABA release but were ineffective in ALS clinical trials (Diana et al, 2017).…”

TDP-43 regulates GAD1 mRNA splicing and GABA signaling in Drosophila CNS

“…Interestingly, our results are in line with other evidences obtained from different ALS models, Boussicault et al 2020 demonstrated that GABA agonists treatment synergistically improved the phenotype in primary cultures of motoneurons derived from SOD1 G93A rat embryos 34 . On the other hand, clinical trials using GABA agonists to treat ALS patients have not yet yielded significant results suggesting that the modulation of GABA neurotransmission alone may not be sufficient to overcome the complete symptoms of the disease 35 . More sophisticated therapies, perhaps combining GABAergic with anti-glutamatergic approaches, might be required to re-stablish the neurotransmitter balance in TDP-43 affected brains.…”

Effects of Sub-Acute Manganese Exposure on Thyroid Hormone and Glutamine (Gln)/Glutamate (Glu)-γ- Aminobutyric Acid (GABA) Cycle in Serum of Rats

“…Thus, impairments of the Gln/Glu–GABA cycle in the brain are associated with movement disorders and motor deficits, and they are involved in the genesis and development of neurodegenerative disease, such as idiopathic PD, Huntington’s disease, amyotrophic lateral sclerosis (ALS), etc. [54,55,56,57]. It is well known that injury of dopaminergic neurons is involved in neurotoxicity induced by Mn [4,56].…”

Enhanced motor cortex output and disinhibition in asymptomatic female mice with C9orf72 genetic expansion

“…Interestingly, in mammalian neurons, the SV2a exhibits a high expression specifically at inhibitory synapses, where it plays an important role in sorting of synaptotagmin I (Bae et al, 2020), thus offering a plausible mechanism that can be responsible for early deficit in GABA release in M1 L5-PYRs of c9-500 mice. Selective targeting of vesicle proteins at inhibitory synapses may represent a good alternative to broad pharmacological manipulations with GABA B receptors, which regulate GABA release but were ineffective in ALS clinical trials (Diana et al, 2017).…”

TDP-43 regulates GAD1 mRNA splicing and GABA signaling in Drosophila CNS

“…Interestingly, our results are in line with other evidences obtained from different ALS models, Boussicault et al 2020 demonstrated that GABA agonists treatment synergistically improved the phenotype in primary cultures of motoneurons derived from SOD1 G93A rat embryos 34 . On the other hand, clinical trials using GABA agonists to treat ALS patients have not yet yielded significant results suggesting that the modulation of GABA neurotransmission alone may not be sufficient to overcome the complete symptoms of the disease 35 . More sophisticated therapies, perhaps combining GABAergic with anti-glutamatergic approaches, might be required to re-stablish the neurotransmitter balance in TDP-43 affected brains.…”

Effects of Sub-Acute Manganese Exposure on Thyroid Hormone and Glutamine (Gln)/Glutamate (Glu)-γ- Aminobutyric Acid (GABA) Cycle in Serum of Rats

“…Thus, impairments of the Gln/Glu–GABA cycle in the brain are associated with movement disorders and motor deficits, and they are involved in the genesis and development of neurodegenerative disease, such as idiopathic PD, Huntington’s disease, amyotrophic lateral sclerosis (ALS), etc. [54,55,56,57]. It is well known that injury of dopaminergic neurons is involved in neurotoxicity induced by Mn [4,56].…”