Neuronal Network Dysfunction in Neurodegenerative Disorders

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About this Research Topic

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Background

The prevalence of neurodegenerative diseases is predicted to increase rapidly in the coming decades. There is a great need for therapies to prevent and/or slow the progression of these disorders as current therapies for most neurodegenerative diseases are symptomatic only. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as amyotrophic lateral sclerosis pose extraordinary challenges for drug development. Several factors are thought to contribute to the neurodegenerative process, such as oxidative stress, excitotoxicity, protein aggregation, vascular dysfunction, and neuroinflammation and these processes culminate in the death of specific neuronal populations, leading to cognitive and/or motor impairments. The pathogenesis of neurodegenerative diseases is also known to be associated with significant dysfunction in multiple neurotransmitter systems, including altered levels of these neurotransmitters and the massive degeneration and remodeling of neuronal networks.

The selective loss of neurons and other mechanisms, such as altered receptor, transporter expression and function lead to dysfunctional network activity in neurodegenerative diseases, and the consequences of these alterations on neural network activity on behavior/cognition and/or motor function are not yet well understood. The underlying mechanisms of selective neuronal and regional vulnerability have been difficult to dissect. Recent developments in whole-genome technologies, in vitro and in vivo disease models, and the extensive examination of anatomical, electrophysiological, and biochemical properties of vulnerable cell populations are beginning to elucidate these basic characteristics of neurodegenerative diseases.

Most recent focus has turned towards therapeutics which target multiple aspects underlying neurodegeneration to ensure future treatment success. The targeting of specific neuronal networks offers many potential therapeutic targets. Drug designs have also shifted from treating neurodegenerative diseases at later stages of disease progression to focusing on preventive strategies at early stages of disease development. Targeting neuronal dysfunction at early stages of these disorders might offer novel and more effective therapeutic options and understanding the neuronal network dysfunction in neurodegenerative disorders will open new insights into the fundamental processes of brain circuit function and remodeling and help to uncover the etiology of these intractable neurological disorders We, therefore, welcome contributions on the advances in every aspect of research (human and non-human) focusing on deciphering the mechanisms of neuronal network dysfunction and exploring the use of new therapeutics with selected neuronal target specificity in neurodegenerative diseases.

Sub-topics may include, but are not limited to:
· Characterization of neural network dysfunction in animal models and human brain
· Mechanisms that contribute to neural network dysfunction in neurodegeneration
· Characterization dysfunction of neurotransmitter systems in neurodegenerative disorders
· Identification of cell-type specific molecular, cellular and network alterations in neurodegeneration
· Translation of neural network dysfunction to human pathology
Therapeutic strategies targeting neural network dysfunction in neurodegenerative disorders

Keywords: Neuronal Network, Neurodegeneration, Alzheimer’s, Parkinson’s, Huntington’s, Neurotransmitters, Excitatory/Inhibitory Balance

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