Biology subjects

Calvo, A. C.

Publications and source records attributed to Calvo, A. C..

2 recordsLinked to original sources

bioRxiv2024

Novel FKBP12 ligand promotes functional improvement in SOD1-G93A ALS mice

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with limited treatment options. ALS pathogenesis involves intricate processes within motor neurons (MNs), characterized by dysregulated Ca2+ influx and buffering in early ALS-affected MNs. This study proposes the modulation of ryanodine receptors (RyRs), key mediators of intracellular Ca2+, as a therapeutic target. A novel class of novel FKBP12 ligands that show activity as cytosolic calcium modulators through stabilizing RyR channel activity, were tested in the SOD1G93A mouse model of ALS. Different outcomes were used to assess treatment efficacy including electrophysiology, histopathology, neuromuscular function, and survival. Among the novel FKBP12 ligands, MP-010 was chosen for its central nervous system availability. Chronic administration of MP-010 to SOD1G93A mice produced a dose-dependent preservation of motor nerve conduction, with the 61 mg/kg dose significantly delaying the onset of motor impairment. This was accompanied by improved motor coordination, increased innervated endplates, and significant preservation of MNs in the spinal cord of treated mice. Notably, MP-010 treatment significantly extended lifespan by an average of 10 days compared to vehicle. In conclusion, FKBP12 ligands, particularly MP-010, exhibit promising neuroprotective effects in ALS, highlighting their potential as novel therapeutic agents. Further investigations into the molecular mechanisms and clinical translatability of these compounds are needed for their application in ALS treatment.

neuroscience↗

bioRxiv2017

Integration of plasticity mechanisms within a single sensory neuron of C. elegans actuates a memory

Neural plasticity--the ability of a neuron to change its cellular properties in response to past experiences--underpins the nervous systems capacity to form memories and actuate behaviors. How different plasticity mechanisms act together in vivo and at a cellular level to transform sensory information into behavior is not well understood. Here we show that in the nematode C. elegans two plasticity mechanisms--sensory adaptation and presynaptic plasticity--act within a single cell to encode thermosensory information and actuate a temperature-preference memory. Sensory adaptation enables the primary thermosensory neuron, AFD, to adjust the temperature range of its sensitivity to the local environment, thereby optimizing its ability to detect temperature fluctuations associated with migration. Presynaptic plasticity transforms this thermosensory information into a behavioral preference by gating synaptic communication between sensory neuron AFD and its postsynaptic partner, AIY. The gating of synaptic communication is regulated at AFD presynaptic sites by the conserved kinase nPKC{varepsilon}. Bypassing or altering AFD presynaptic plasticity predictably changes the learned behavioral preferences without affecting sensory responses. Our findings indicate that two distinct and modular neuroplasticity mechanisms function together within a single sensory neuron to encode multiple components of information required to enact thermotactic behavior. The integration of these plasticity mechanisms result in a single-cell logic system that can both represent sensory stimuli and guide memory-based behavioral preference.

neuroscience↗