ChanFAD: A Functional Annotation Database for Ion Channels.

Ion channels are integral membrane protein complexes critical for regulation of membrane potential, cell volume, and other signaling events. As complex molecular assemblies with many interacting partners, ion channels have multiple structural and functional domains. While channel sequence and functional data are readily available across multiple online resources, there is an unmet need for functional annotation directly relating primary sequence information, 2D interactions, and three-dimensional protein structure. To this end, we present ChanFAD (Channel Functional Annotation Database), to provide the research community with a centralized resource for ion channel structure and functional data. ChanFAD provides functional annotation of PDB structures built on the National Center for Biotechnology Information's iCn3D structure viewing tool while providing additional information such as primary sequence, organism, and relevant links to other databases. Here we provide a brief tour of ChanFAD functionality while showing example use cases involving drug-channel interactions and structural changes based on mutation. ChanFAD is freely available and can be accessed at https://www.chanfad.org/.

Visual imaging as a predictor of neurodegeneration in experimental autoimmune demyelination and multiple sclerosis.

Thalamic volume is associated with clinical disability in multiple sclerosis (MS) and is vulnerable to secondary neurodegeneration due to its extensive connectivity throughout the central nervous system (CNS). Using a model of autoimmune demyelination that exhibits CNS-infiltrating immune cells in both spinal cord white matter and optic nerve, we sought to evaluate neurodegenerative changes due to lesions affecting the spino- and retino-thalamic pathways. We found comparable axonal loss in spinal cord white matter and optic nerve during the acute phase of disease consistent with synaptic loss, but not neuronal cell body loss in the thalamic nuclei that receive input from these discrete pathways. Loss of spinal cord neurons or retinal ganglion cells retrograde to their respective axons was not observed until the chronic phase of disease, where optical coherence tomography (OCT) documented reduced inner retinal thickness. In patients with relapsing-remitting MS without a history of optic neuritis, OCT measures of inner retinal volume correlated with retino-thalamic (lateral geniculate nucleus) and spino-thalamic (ventral posterior nucleus) volume as well as neuroperformance measures. These data suggest retinal imaging may serve as an important noninvasive predictor of neurodegeneration in MS.