Nrf2/Wnt resilience orchestrates rejuvenation of glia-neuron dialogue in Parkinson’s disease
Fecha
2020Autor
Marchetti, Bianca
Documentos PDF
Resumen
Oxidative stress and inflammation have long been recognized to contribute to Parkinson’s disease (PD), a
common movement disorder characterized by the selective loss of midbrain dopaminergic neurons (mDAn)
of the substantia nigra pars compacta (SNpc). The causes and mechanisms still remain elusive, but a
complex interplay between several genes and a number of interconnected environmental factors, are chiefly
involved in mDAn demise, as they intersect the key cellular functions affected in PD, such as the
inflammatory response, mitochondrial, lysosomal, proteosomal and autophagic functions. Nuclear factor
erythroid 2 -like 2 (NFE2L2/ Nrf2), the master regulator of cellular defense against oxidative stress and
inflammation, and Wingless (Wnt)/β-catenin signaling cascade, a vital pathway for mDAn neurogenesis and
neuroprotection, emerge as critical intertwinned actors in mDAn physiopathology, as a decline of an
Nrf2/Wnt/β-catenin prosurvival axis with age underlying PD mutations and a variety of noxious
environmental exposures drive PD neurodegeneration. Unexpectedly, astrocytes, the so-called “star-shaped”
cells, harbouring an arsenal of “beneficial” and “harmful” molecules represent the turning point in the
physiopathological and therapeutical scenario of PD. Fascinatingly, “astrocyte’s fil rouge” brings back to
Nrf2/Wnt resilience, as boosting the Nrf2/Wnt resilience program rejuvenates astrocytes, in turn (i)
mitigating nigrostriatal degeneration of aged mice, (ii) reactivating neural stem progenitor cell proliferation
and neuron differentiation in the brain and (iii) promoting a beneficial immunomodulation via bidirectional
communication with mDAns. Then, through resilience of Nrf2/Wnt/β-catenin anti-ageing, prosurvival and
proregenerative molecular programs, it seems possible to boost the inherent endogenous self-repair
mechanisms. Here, the cellular and molecular aspects as well as the therapeutical options for rejuvenating
glia-neuron dialogue will be discussed together with major glial-derived mechanisms and therapies that will
be fundamental to the identification of novel diagnostic tools and treatments for neurodegenerative diseases
(NDs), to fight ageing and nigrostriatal DAergic degeneration and promote functional recovery.
Palabras clave
Glia-neuron crosstalk; Parkinson’s disease; Gene-environment ineteractions; Nrf2 signaling; Wnt signaling; Ageing; Oxidative/inflammatory stress; Astrocyte therapiesEnlace al recurso
https://doi.org/10.1016/j.redox.2020.101664Colecciones
Estadísticas Google Analytics
Comentarios
Respuesta Comentario Repositorio Expeditio
Gracias por tomarse el tiempo para darnos su opinión.