Work

Restoring nitric oxide/Peroxynitrite equilibrium in impaired human neural progenitor cells: Nanomedical approaches and their potential impact on neurodegenerative disease treatment

Year: 2025

Type: article

Abstract: Nitric oxide (NO), an essential inorganic signaling molecule, involved in many physiological processes and has promising therapeutic potential Its oxidation product, peroxynitrite (ONOO ¯ ), is cytotoxic, and elevated ONOO ¯ levels induce nitroxidative stress, a factor implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). Through pharmacological modulation of NO and ONOO ¯ levels in human neural progenitor cell (hNPCs), this study explores the potential pharmaceutical interventions targeting the NO and the neuronal nitric oxide synthase (nNOS) pathway, (NO/nNOS), to prevent or reduce AD progression by restoring the [NO]/[ONOO ¯ ] balance. To achieve this, metalloporphyrin nanosensors have been effectively employed for real-time, in-situ measurement of NO and ONOO ¯ concentrations (200–300 nm diameter) were applied and precisely positioned 4–5 ± 1 μm from hNPCs membranes, enabling precise investigation of the [NO]/[ONOO ¯ ] ratio. The [NO]/[ONOO ¯ ] ratio emerged as a critical biomarker for the evaluation of nNOS coupling/uncoupling to the hNPC functioning/dysfunction. In healthy cells, this ratio was around 0.25 ± 0.005, While dysfunctional hNPCs treated to amyloid beta 42 (Aβ 42 )—a hallmark of AD—caused a dramatic 94 % drop, signaling severe cellular dysfunction. Based on these findings, potential pharmacological interventions have been proposed to prevent or reduce AD progression by restoring the [NO]/[ONOO ¯ ] balance. Notably, a co-treatment of sepiapterin (SEP), a cofactor precursor for NO synthesis, with VAS 2870 (an NADPH oxidase inhibitor) partially restored the ratio to 0.1, indicating improved nNOS function.

Source: Journal of Inorganic Biochemistry

DOI: 10.1016/j.jinorgbio.2025.113073

Authors: Nouf Alsiraey, Howard D. Dewald

Institutions: Northern Border University, Ohio University

Language: English

Topic: Nitric Oxide and Endothelin Effects

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,220