GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, brain atrophy due to neuronal and synapse loss, and formation of two pathological lesions: extracellular amyloid plaques, composed largely of amyloid-beta peptide (Aβ), and neurofibrillary tangles...
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2014
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| Acceso en línea: | http://repository.urosario.edu.co/handle/10336/19571 https://doi.org/10.3389/fncel.2014.00167 |
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ir-10336-195712020-05-06T05:15:46Z GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease Nava-Mesa, Mauricio O. Jiménez-Díaz, Lydia Yajeya, Javier Navarro-Lopez, Juan D. Grupo de Investigación de Neurociencias de la Universidad del Rosario (NEUROS) septohippocampal system amyloid-β peptide excitatory and inhibitory neurotransmission Enfermedades Sistema Septohipocampal Péptido amiloide β Neurotransmisión excitatoria e inhibitoria Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, brain atrophy due to neuronal and synapse loss, and formation of two pathological lesions: extracellular amyloid plaques, composed largely of amyloid-beta peptide (Aβ), and neurofibrillary tangles formed by intracellular aggregates of hyperphosphorylated tau protein. Lesions mainly accumulate in brain regions that modulate cognitive functions such as the hippocampus, septum or amygdala. These brain structures have dense reciprocal glutamatergic, cholinergic, and GABAergic connections and their relationships directly affect learning and memory processes, so they have been proposed as highly susceptible regions to suffer damage by Aβ during AD course. Last findings support the emerging concept that soluble Aβ peptides, inducing an initial stage of synaptic dysfunction which probably starts 20–30 years before the clinical onset of AD, can perturb the excitatory–inhibitory balance of neural circuitries. In turn, neurotransmission imbalance will result in altered network activity that might be responsible of cognitive deficits in AD. Therefore, Aβ interactions on neurotransmission systems in memory-related brain regions such as amygdaloid complex, medial septum or hippocampus are critical in cognitive functions and appear as a pivotal target for drug design to improve learning and dysfunctions that manifest with age. Since treatments based on glutamatergic and cholinergic pharmacology in AD have shown limited success, therapies combining modulators of different neurotransmission systems including recent findings regarding the GABAergic system, emerge as a more useful tool for the treatment, and overall prevention, of this dementia. In this review, focused on inhibitory systems, we will analyze pharmacological strategies to compensate neurotransmission imbalance that might be considered as potential therapeutic interventions in AD. 2014 2019-05-06T14:56:03Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 1662-5102 http://repository.urosario.edu.co/handle/10336/19571 https://doi.org/10.3389/fncel.2014.00167 eng http://www.sherpa.ac.uk/romeo/search.php?issn=1662-5102&la=es info:eu-repo/semantics/openAccess application/pdf |
| institution |
EdocUR - Universidad del Rosario |
| collection |
DSpace |
| language |
Inglés (English) |
| topic |
septohippocampal system amyloid-β peptide excitatory and inhibitory neurotransmission Enfermedades Sistema Septohipocampal Péptido amiloide β Neurotransmisión excitatoria e inhibitoria |
| spellingShingle |
septohippocampal system amyloid-β peptide excitatory and inhibitory neurotransmission Enfermedades Sistema Septohipocampal Péptido amiloide β Neurotransmisión excitatoria e inhibitoria Nava-Mesa, Mauricio O. Jiménez-Díaz, Lydia Yajeya, Javier Navarro-Lopez, Juan D. GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease |
| description |
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, brain atrophy due to neuronal and synapse loss, and formation of two pathological lesions: extracellular amyloid plaques, composed largely of amyloid-beta peptide (Aβ), and neurofibrillary tangles formed by intracellular aggregates of hyperphosphorylated tau protein. Lesions mainly accumulate in brain regions that modulate cognitive functions such as the hippocampus, septum or amygdala. These brain structures have dense reciprocal glutamatergic, cholinergic, and GABAergic connections and their relationships directly affect learning and memory processes, so they have been proposed as highly susceptible regions to suffer damage by Aβ during AD course. Last findings support the emerging concept that soluble Aβ peptides, inducing an initial stage of synaptic dysfunction which probably starts 20–30 years before the clinical onset of AD, can perturb the excitatory–inhibitory balance of neural circuitries. In turn, neurotransmission imbalance will result in altered network activity that might be responsible of cognitive deficits in AD. Therefore, Aβ interactions on neurotransmission systems in memory-related brain regions such as amygdaloid complex, medial septum or hippocampus are critical in cognitive functions and appear as a pivotal target for drug design to improve learning and dysfunctions that manifest with age. Since treatments based on glutamatergic and cholinergic pharmacology in AD have shown limited success, therapies combining modulators of different neurotransmission systems including recent findings regarding the GABAergic system, emerge as a more useful tool for the treatment, and overall prevention, of this dementia. In this review, focused on inhibitory systems, we will analyze pharmacological strategies to compensate neurotransmission imbalance that might be considered as potential therapeutic interventions in AD. |
| author2 |
Grupo de Investigación de Neurociencias de la Universidad del Rosario (NEUROS) |
| author_facet |
Grupo de Investigación de Neurociencias de la Universidad del Rosario (NEUROS) Nava-Mesa, Mauricio O. Jiménez-Díaz, Lydia Yajeya, Javier Navarro-Lopez, Juan D. |
| format |
Artículo (Article) |
| author |
Nava-Mesa, Mauricio O. Jiménez-Díaz, Lydia Yajeya, Javier Navarro-Lopez, Juan D. |
| author_sort |
Nava-Mesa, Mauricio O. |
| title |
GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease |
| title_short |
GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease |
| title_full |
GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease |
| title_fullStr |
GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease |
| title_full_unstemmed |
GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimer’s disease |
| title_sort |
gabaergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of alzheimer’s disease |
| publishDate |
2014 |
| url |
http://repository.urosario.edu.co/handle/10336/19571 https://doi.org/10.3389/fncel.2014.00167 |
| _version_ |
1666561413415436288 |
| score |
12,131701 |