RT info:eu-repo/semantics/article
T1 Vulnerability of mesostriatal dopaminergic neurons in Parkinson's disease
A1 Castro Hernández, Javier Rafael
A1 González-Hernández, Tomás
A1 Cruz-Muros, Ignacio
A1 Salas-Hernández, Josmar
A2 Vulnerabilidad y plasticidad neuronal
K1 Parkinson’s disease
K1 Neurodegeneration
K1 Aging
K1 Nigrostriatal
AB The term vulnerability was first associated with the midbrain dopaminergic neurons 85 yearsago, 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 postencephalitic Parkinson’s disease (PD). A few years later, Hassler (1938) showed that degenerationis more intense in the ventral tier of the substantia nigra compacta than in its dorsal tier andthe ventral tegmental area (VTA), outlining the concept of differential vulnerability of midbraindopaminergic (DA-) neurons. Nowadays, we know that other neuronal groups degenerate inPD, but the massive loss of nigral DA-cells is its pathological hallmark, having a pivotal positionin the pathophysiology of the disease as it is responsible for the motor symptoms. Data fromhumans as well as cellular and animal models indicate that DA-cell degeneration is a complexprocess, probably precipitated by the convergence of different risk factors, mediated by oxidativestress, and involving pathogenic factors arising within the DA-neuron (intrinsic factors), and fromits environment and distant interconnected brain regions (extrinsic factors). In light of currentdata, intrinsic factors seem to be preferentially involved in the first steps of the degenerativeprocess, and extrinsic factors in its progression. A controversial issue is the relative weight of theimpairment of common cell functions, such as energy metabolism and proteostasis, and specificdopaminergic functions, such as pacemaking activity and DA handling, in the pathogenesis ofDA-cell degeneration. Here we will review the current knowledge about the relevance of thesefactors at the beginning and during the progression of PD, and in the differential vulnerabilityof midbrain DA-cells.
SN 1662-5129
YR 2010
FD 2010
LK http://riull.ull.es/xmlui/handle/915/34754
UL http://riull.ull.es/xmlui/handle/915/34754
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 25-nov-2024