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Uncovering novel actors in astrocyte–neuron crosstalk in P arkinson's disease: the W nt/β‐catenin signaling cascade as the common final pathway for neuroprotection and self‐repair
Author(s) -
Marchetti Bianca,
L'Episcopo Francesca,
Morale Maria Concetta,
Tirolo Cataldo,
Testa Nuccio,
Caniglia Salvo,
Serapide Maria Francesca,
Pluchino Stefano
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12166
Subject(s) - neuroscience , neuroprotection , neurodegeneration , substantia nigra , pars compacta , biology , dopaminergic , dopamine , medicine , disease
Parkinson's disease ( PD ) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic ( DA ergic) neuronal cell bodies in the substantia nigra pars compacta and gliosis. The cause and mechanisms underlying the demise of nigrostriatal DA ergic neurons are ill‐defined, but interactions between genes and environmental factors are recognized to play a critical role in modulating the vulnerability to PD . Current evidence points to reactive glia as a pivotal factor in PD pathophysiology, playing both protective and destructive roles. Here, the contribution of reactive astrocytes and their ability to modulate DA ergic neurodegeneration, neuroprotection and neurorepair in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine ( MPTP ) rodent model of PD will be discussed in the light of novel emerging evidence implicating wingless‐type mouse mammary tumor virus integration site (Wnt)/β‐catenin signaling as a strong candidate in MPTP ‐induced nigrostriatal DA ergic plasticity. In this work, we highlight an intrinsic W nt1/frizzled‐1/β‐catenin tone that critically contributes to the survival and protection of adult midbrain DA ergic neurons, with potential implications for drug design or drug action in PD . The dynamic interplay between astrocyte‐derived factors and neurogenic signals in MPTP ‐induced nigrostriatal DA ergic neurotoxicity and repair will be summarized, together with recent findings showing a critical role of glia–neural stem/progenitor cell ( NPC ) interactions aimed at overcoming neurodegeneration and inducing neurorestoration. Understanding the intrinsic plasticity of nigrostriatal DA ergic neurons and deciphering the signals facilitating the crosstalk between astrocytes, microglia, DA ergic neurons and NPC s may have major implications for the role of stem cell technology in PD , and for identifying potential therapeutic targets to induce endogenous neurorepair.