Role of extracellular trafficking of neuroglobin in neurodegeneration and neuroprotection

Cellular survival relies on the regulation of growth, metabolism, and stress responses. Neurons, due to their post-mitotic nature, are particularly vulnerable and irreplaceable. In fact, in response to stress, they activate protective mechanisms, but excessive stress can lead to apoptosis. This progressive neuronal loss underlies neurodegeneration, contributing to aging and disorders such as Alzheimer’s, Parkinson’s, Huntington’s diseases and amyotrophic lateral sclerosis (Kole et al., 2013; Wilson III et al., 2023). Although the exact causes of these diseases remain unclear, they share common features including oxidative stress, mitochondrial dysfunction, and the accumulation of misfolded proteins, which induce endoplasmic reticulum (ER) stress and disrupt cellular homeostasis. Furthermore, neurodegenerative diseases are characterized by impaired autophagy, altered glucose metabolism, genetic mutations, and structural changes in neurons. Chronic inflammation exacerbates neuronal damage, acceleratin