Publications by authors named "M D'Adamo"
Generation of human induced pluripotent stem cells (iPSCs) through reprogramming was a transformational change in the field of regenerative medicine that led to new possibilities for drug discovery and cell replacement therapy. Several protocols have been established to differentiate hiPSCs into neuronal lineages. However, low differentiation efficiency is one of the major drawbacks of these approaches.
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- Loss-of-function mutations in the Kv1.1 gene lead to episodic ataxia type 1 (EA1), causing symptoms like cerebellar dysfunction, ataxic attacks, muscle cramps, and epilepsy.
- Current treatments lack drugs that can counteract functional defects in Kv1.1 channels, making precision medicine for EA1 unfeasible.
- The study found that niflumic acid (NFA), an existing analgesic, enhances Kv1.1 channel activity and mitigates EA1 symptoms, showing promise as a therapeutic agent and a model for drug discovery.
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- Locus coeruleus (LC) neurons influence many physiological functions in the brain, but the role of ERG K+ channels in these neurons had not been fully explored until now.
- Recent studies revealed that ERG-1A, ERG-1B, ERG-2, and ERG-3 channels are highly expressed in LC neurons of mice, indicating their potential significance.
- Blocking ERG channels with the drug WAY-123,398 increased firing activity in LC neurons, suggesting that these channels are critical for regulating neuronal firing patterns, which may be linked to various behaviors and disorders.
Astrocytes, the main glial cells of the central nervous system, play a key role in brain volume control due to their intimate contacts with cerebral blood vessels and the expression of a distinctive equipment of proteins involved in solute/water transport. Among these is MLC1, a protein highly expressed in perivascular astrocytes and whose mutations cause megalencephalic leukoencephalopathy with subcortical cysts (MLC), an incurable leukodystrophy characterized by macrocephaly, chronic brain edema, cysts, myelin vacuolation, and astrocyte swelling. Although, in astrocytes, MLC1 mutations are known to affect the swelling-activated chloride currents (ICl,) mediated by the volume-regulated anion channel (VRAC), and the regulatory volume decrease, MLC1's proper function is still unknown.
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