Molecular Mechanisms Underlying Synaptic and Axon Degeneration in Neurodegenerative Diseases

Adult onset neurodegenerative diseases include a heterogeneous group of disorders characterized by dysfunction and progressive degeneration of selected neuronal populations. Although their etiology is heterogeneous, they all share some common characteristics including a progressive development in the severity of clinical symptoms that is associated with the decline of neuronal functions. A central theme underlying these processes is selective synaptic dysfunction and subsequent neuronal disconnection, followed by a progressive dying-back pattern of axonal degeneration. Months, or even years, after the first signs of pathology, neuronal death signaling pathways are then activated leading to neuronal loss. Despite decades of intense research and a large body of cellular and molecular information, the molecular mechanisms driving those pathological features remain elusive. The lack of clear molecular mechanisms underlying these neuropathies remains a major impediment in developing effective therapeutic interventions that could stop or delay the progression of these diseases.

The goal of this Research Topic is to coalesce work by leaders from the different fields of cellular and molecular neurobiology. Our aim is to shed light on the pathological mechanisms underlying progressive synaptic and axonal degeneration displayed in many adult onset neurological disorders, including but not limited to: Alzheimer’s, Parkinson’s, Huntington’s, amyotrophic lateral sclerosis, Hereditary spastic paraplegia, traumatic brain injury, frontotemporal dementia, Tauopathies, glaucoma, motor neuron diseases, lysosomal storage diseases, and diseases involving myelin. Focusing on disease-specific mechanisms responsible for the initiation of neuronal dysfunction and loss should facilitate the development of therapies aimed to preserve neuronal function and eventually to preserve the different neuronal populations affected in each disease.

We seek contributions to this important topic including original research articles, reviews and mini reviews. The articles focused on the following topics, but not restrictive to, are welcome:

• Molecular mechanisms of synaptic dysfunction
• Cellular and molecular mechanisms underlying altered axonal transport
• Mechanisms underlying abnormal synaptic function in adult onset neurodegenerative diseases
• Alterations in signaling pathways associated with dying-back neuropathies
• Death signaling pathways in neurodegeneration
• Mechanisms underlying axonal degeneration
• Cellular and molecular mechanisms associated to alterations in neuronal cytoskeleton
• Molecular mechanisms driving neuronal morphology and neuronal connectivity by neurotrophic factors and their receptors
• Pathogenic mechanisms of lysosome and mitochondria autophagy
• Molecular mechanisms that regulate axonal or synaptic function through myelination and/or other glial functions