Cited by 65Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingDeep Brain Stimulation and Movement Disorders

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Vulnerability of mesostriatal dopaminergic neurons in Parkinson’s disease

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González-Hernández, Tomás·2010·Frontiers in Neuroanatomy

DOI 10.3389/fnana.2010.00140PMC PMC2978035

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Abstract

The term vulnerability was first associated with the midbrain dopaminergic neurons 85 years ago, before they were identified as monoaminergic neurons, when Foix and Nicolesco (1925) reported the loss of neuromelanin containing neurons in the midbrain of patients with post-encephalitic Parkinson's disease (PD). A few years later, Hassler (1938) showed that degeneration is more intense in the ventral tier of the substantia nigra compacta than in its dorsal tier and the ventral tegmental area (VTA), outlining the concept of differential vulnerability of midbrain dopaminergic (DA-) neurons. Nowadays, we know that other neuronal groups degenerate in PD, but the massive loss of nigral DA-cells is its pathological hallmark, having a pivotal position in the pathophysiology of the disease as it is responsible for the motor symptoms. Data from humans as well as cellular and animal models indicate that DA-cell degeneration is a complex process, probably precipitated by the convergence of different risk factors, mediated by oxidative stress, and involving pathogenic factors arising within the DA-neuron (intrinsic factors), and from its environment and distant interconnected brain regions (extrinsic factors). In light of current data, intrinsic factors seem to be preferentially involved in the first steps of the degenerative process, and extrinsic factors in its progression. A controversial issue is the relative weight of the impairment of common cell functions, such as energy metabolism and proteostasis, and specific dopaminergic functions, such as pacemaking activity and DA handling, in the pathogenesis of DA-cell degeneration. Here we will review the current knowledge about the relevance of these factors at the beginning and during the progression of PD, and in the differential vulnerability of midbrain DA-cells.

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Sorted by citations

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“Tretiakoff named the eponymous Lewy body inclusions in honor of Lewy’s work and a more detailed description of PD pathology by Foix & Nicolesco subsequently identified the specific loss of pigmented, neuromelanin containing neurons in the SN (Gonzalez-Hernandez et al. 2010).”
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Local cues establish and maintain region-specific phenotypes of basal ganglia microglia
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“Although dopaminergic neurons throughout the midbrain degenerate during Parkinson’s disease, death of SNc dopamine neurons is more pronounced (González-Hernández et al., 2010).”
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“There is evidence that the dopaminergic neurons of the SNpc are vulnerable to oxidative damage, as they present low levels of antioxidant enzymes, such as glutathione peroxidase, and high levels of pro-oxidants, such as free iron and neuromelanin (González-Hernández et al., 2010).”
Background

See all 65

Authors: González-Hernández, T.
Venue: Frontiers in Neuroanatomy
Publisher: Frontiers Media SA
Published: 2010
Volume: 4
Pages: 140-140
ISSN: 1662-5129 (ISSN-L)
DOI: 10.3389/fnana.2010.00140
PMC: PMC2978035
OpenAlex: W2123571361
Cited by: 65
References: 263
Citations by year: 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 10 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 2 · 2012: 11
FWCI: 3.44
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Neuroanatomy (publishedVersion, cc-by)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Fundación Canaria de Investigación y Salud
Department of Science and Technology, Ministry of Science and Technology, India
Ministerio de Ciencia e Innovación
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
Instituto de Salud Carlos III
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
Keywords: Parkinson's disease, substantia nigra pars compacta, ventral tegmental area, oxidative stress, intrinsic and extrinsic risk factors, energy metabolism, proteostasis

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Vulnerability of mesostriatal dopaminergic neurons in Parkinson’s disease

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