{"title":"Overview","authors":"E. Benarroch","doi":"10.1093/MED/9780190948894.003.0001","DOIUrl":"https://doi.org/10.1093/MED/9780190948894.003.0001","url":null,"abstract":"The nervous system consists of neurons, glial cells, blood vessels, and extracellular matrix. Neurons are electrically excitable cells and are primarily responsible for initiation, processing, and transmission of information. However, their function is affected by their reciprocal interactions with glial cells, which contribute to development, survival, and plasticity of synaptic connections and shape the activity of neuronal ensembles and systems critical for cognition and behavior. Advances in molecular, cellular, and electrophysiological approaches have provided major insight not only in normal function of neurons and glial cells but also in the pathophysiology of neurologic diseases at the molecular, synaptic, cellular network, and system levels.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121097521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Basal Ganglia Circuits","authors":"E. Benarroch","doi":"10.1093/MED/9780190948894.003.0034","DOIUrl":"https://doi.org/10.1093/MED/9780190948894.003.0034","url":null,"abstract":"The basal ganglia circuits have a central role in reward-based action learning, goal-directed behaviors; and habit formation. These processes largely depend on dopamine signals in the striatum, which controls the activity of the other components of the basal ganglia circuits, including the globus pallidus, substantia nigra, and subthalamic nucleus. Reward signals trigger a dopamine peak in the striatum, which promotes selection of a rewarding action and prevents initiation of competing actions. Dopamine also prevents abnormal synchronized oscillatory activity in the basal ganglia circuits. Loss of dopaminergic signaling triggers changes that underlie the motor manifestations of Parkinson disease (PD), including akinesia and levodopa-induced dyskinesia. Imbalance between dopaminergic and cholinergic signaling in the striatum underlies hyperkinetic movement disorders.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124514863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proteostasis","authors":"Eduardo E. Benarroch","doi":"10.1093/med/9780190948894.003.0006","DOIUrl":"https://doi.org/10.1093/med/9780190948894.003.0006","url":null,"abstract":"Normal cell function and survival depend on carefully regulated synthesis, folding, trafficking, and degradation of proteins. The balance among these processes is referred to as proteostasis. Proteins undergo maturation and folding in the endoplasmic reticulum. This process is error-prone and can be affected by mutations, errors during transcription or translation, and cellular stressors. Several interacting mechanisms, including the endoplasmic reticulum stress response, the unfolded protein response, and degradation by the ubiquitin-proteasome and the autophagosome-lysosome systems prevent the accumulation of misfolded proteins. Protein misfolding and incorporation into fibrillary structures is a fundamental mechanism of many neurodegenerative disorders. Degeneration results from toxic gain-of-function of the intermediate fibril monomers, promoting the formation of aggregates and initiating a cascade of protein–protein interactions leading to neuronal dysfunction and death, associated with neuroinflammation. These protein aggregates may serve as templates or seeds to elicit aggregation of their respective normal endogenous partners in neighboring cells, leading to disease propagation.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128348028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Intracellular Signaling","authors":"E. Benarroch","doi":"10.1002/047146158x.ch16","DOIUrl":"https://doi.org/10.1002/047146158x.ch16","url":null,"abstract":"Interactions between cells in the nervous system are bidirectional and involve a large number of chemical signals. These interactions occur via receptors located at presynaptic terminals, postsynaptic processes, or at a distance. Activation of membrane receptors by neurotransmitters, growth factors, cytokines, or other extracellular signals triggers downstream intracellular signaling pathways that affect a wide range of cellular functions. The final common mechanism is regulation of the state of phosphorylation of multiple crucial proteins in membranes, cytosol, cytoskeleton, and nucleus. The coupling between extracellular signals and these intracellular responses depends on transduction pathways that include G proteins that function as molecular switches; second messenger molecules such as cyclic nucleotides and phosphatidylinositol metabolites; intracellular calcium transients; and activation of protein kinases and phosphatases. Alterations of these fundamental cellular mechanisms provide the bases for a large number of disorders of the nervous system as well as potential therapeutic targets.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122865219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vesicular Trafficking","authors":"E. Benarroch","doi":"10.1093/med/9780190948894.003.0007","DOIUrl":"https://doi.org/10.1093/med/9780190948894.003.0007","url":null,"abstract":"Normal cell function depends on the appropriate synthesis, maturation, sorting, and delivery of fully processed proteins and other macromolecules to specific intracellular compartments; uptake of material from the cell exterior; and regulated intracellular processing and degradation of proteins, lipids, complex carbohydrates, abnormal aggregates, and senescent organelles. These fundamental functions involve secretory, endocytic, and autophagic pathways. The secretory pathway is responsible for protein maturation, sorting, and delivery of transmembrane and secreted proteins from their site of synthesis to their final destinations. Synaptic vesicle exocytosis is a special form of secretion that allows rapid communication between neurons. The endocytic pathway starts with the internalization of material via endosomes. Endosomal content can be transported back to the cell body, recycled to cell compartments, or delivered for degradation by the lysosome. Abnormal protein aggregates or damaged organelles undergo autophagy, which involves formation of an autophagosome and degradation by the lysosome. Impaired vesicular trafficking is a fundamental mechanism in a large number of neurodegenerative disorders, including hereditary spastic paraplegia, lower motor neuron syndromes, and Parkinson disease.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128759198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Language","authors":"Eduardo E. Benarroch","doi":"10.1093/med/9780190948894.003.0041","DOIUrl":"https://doi.org/10.1093/med/9780190948894.003.0041","url":null,"abstract":"Language, speech, and semantic knowledge are fundamental cognitive functions critical for human communication and knowledge of the world. Language comprehension and production involve core areas in the left temporoparietal cortex and inferior frontal gyrus that participate in separate but interacting networks for semantic and syntactic processing. Voice and speech production are controlled by separate corticobulbar systems that are hierarchically organized. Semantic knowledge about world objects and their action primarily involves ventrolateral portions of the anterior temporal lobe. Disturbances of these processes manifest with different forms of primary progressive aphasia, apraxia of speech, or semantic variant primary progressive aphasia.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133957971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Monoaminergic Systems","authors":"E. Benarroch","doi":"10.1093/med/9780190948894.003.0020","DOIUrl":"https://doi.org/10.1093/med/9780190948894.003.0020","url":null,"abstract":"Central monoaminergic systems are involved in behavioral arousal, attention, motivation, and control of motor, nociceptive, and autonomic processing. They include dopaminergic, noradrenergic, serotonergic, and histaminergic neurons with cell bodies in restricted areas of the brainstem and hypothalamus and widespread axonal projections targeting multiple brain regions. Via their multiple receptor mechanisms, these systems exert a complex and behavioral-state-dependent modulation of excitability of neurons and neuronal networks. In the periphery, norepinephrine is the major neurotransmitter of the sympathetic system. Monoaminergic systems are affected in genetic disorders of monoamine metabolism, neurodegenerative conditions, and psychiatric disorders. These systems are also a major target for pharmacologic therapy.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123346347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytoskeleton","authors":"Eduardo E. Benarroch","doi":"10.1093/med/9780190948894.003.0008","DOIUrl":"https://doi.org/10.1093/med/9780190948894.003.0008","url":null,"abstract":"The cytoskeleton consists primarily of microfilaments, microtubules, and intermediate filaments. Actin microfilaments have major role in growth, maintenance, and dynamic changes of growth cones and dendrites; stabilization of proteins at specific membrane locations; and vesicle dynamics during endocytosis and exocytosis. Microtubules provide the major tracks for intracellular transport and local cues for positioning of mitochondria and other organelles. The intermediate filaments in neurons are the neurofilaments that have a major role in regulating axonal caliber and mechanical stability. Glial fibrillary acid protein is a primary component of intermediate filaments in astrocytes. Nuclear lamins participate in regulation of the chromatin organization, trafficking of transcription factors across the nuclear envelope, and transduction of mechanical signals. Mutations affecting these cytoskeletal proteins produce a wide range of neurologic disorders, including neurodevelopmental disorders, peripheral neuropathies, myopathies, and leukodystrophy. All components of the cytoskeleton are involved in adult-onset neurodegenerative disorders.","PeriodicalId":196283,"journal":{"name":"Neuroscience for Clinicians","volume":"61 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125065382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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