Author
Paola Soldani
Bio: Paola Soldani is an academic researcher from University of Pisa. The author has contributed to research in topics: Parkinson's disease & Pars compacta. The author has an hindex of 18, co-authored 65 publications receiving 1033 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: This review analyzes the latest data obtained from experimental parkinsonism indicating that, the loss of norepinephrine in Parkinson's disease might worsen the dopamine nigrostriatal damage.
232 citations
TL;DR: PC12 inclusions, similar to those observed in nigral neurones, were exclusively localized in the cytoplasm and stained for α‐synuclein, and time‐dependent experiments showed that inclusions underwent a progressive fusion of the external membranes and developed an electrodense core.
Abstract: Mice treated with the psychostimulant methamphetamine (MA) showed the appearance of intracellular inclusions in the nucleus of medium sized striatal neurones and cytoplasm of neurones of the substantia nigra pars compacta but not in the frontal cortex. All inclusions contained ubiquitin, the ubiquitin activating enzyme (E1), the ubiquitin protein ligase (E3-like, parkin), low and high molecular weight heat shock proteins (HSP 40 and HSP 70). Inclusions found in nigral neurones stained for alpha-synuclein, a proteic hallmark of Lewy bodies that are frequently observed in Parkinson's disease and other degenerative disorders. However, differing from classic Lewy bodies, MA-induced neuronal inclusions appeared as multilamellar bodies resembling autophagic granules. Methamphetamine reproduced this effect in cultured PC12 cells, which offered the advantage of a simple cellular model for the study of the molecular determinants of neuronal inclusions. PC12 inclusions, similar to those observed in nigral neurones, were exclusively localized in the cytoplasm and stained for alpha-synuclein. Time-dependent experiments showed that inclusions underwent a progressive fusion of the external membranes and developed an electrodense core. Inhibition of dopamine synthesis by alpha-methyl-p-tyrosine (alphaMpT), or administering the antioxidant S-apomorphine largely attenuated the formation of inclusions in PC12 cells exposed to MA. Inclusions were again observed when alphaMpT-treated cells were loaded with l-DOPA, which restored intracellular dopamine levels.
125 citations
TL;DR: It is hypothesized that an imbalance of redox cell status is responsible for the induction and persistence of noise-induced cellular damage in rat adrenal gland.
Abstract: Loud noise is generally considered an environmental stressor causing negative effects on acoustic, cardiovascular, nervous, and endocrine systems. In this study, we investigated the effects of noise exposure on DNA integrity in rat adrenal gland evaluated by the comet assay. The exposure to loud noise (100 dBA) for 12 hr caused a significant increase of DNA damage in the adrenal gland. Genetic alterations did not decrease 24 hr after the cessation of the stimulus. We hypothesize that an imbalance of redox cell status is responsible for the induction and persistence of noise-induced cellular damage.
42 citations
TL;DR: Evidence is provided that in both genetic and sporadic amyotrophic lateral sclerosis (ALS, the most common motor neuron disorder) a defect in the autophagy machinery is common and represents an important target when developing novel treatments in ALS.
Abstract: In the present review a large amount of experimental and clinical studies on ALS are discussed in an effort to dissect common pathogenic mechanisms which may provide novel information and potential therapeutic strategies for motor neuron degeneration.Protein clearing systems play a critical role in motor neuron survival during excitotoxic stress, aging and neurodegenerative disorders. Among various mechanisms which clear proteins from the cell recent studies indicate autophagy as the most prominent pathway to promote survival of motor neurons.Autophagy regulates the clearance of damaged mitochondria, endoplasmic reticulum and misfolded proteins in eukaryotic cells. Upon recruitment of the autophagy pathway, an autophagosome is produced and directed towards lysosomal degradation.Here we provide evidence that in both genetic and sporadic amyotrophic lateral sclerosis (ALS, the most common motor neuron disorder) a defect in the autophagy machinery is common. In fact, swollen, disrupted mitochondria and intracellular protein aggregates accumulate within affected motor neurons. These structures localize within double membrane vacuoles, autophagosomes, which typically cluster in perinuclear position. In keeping with this, when using autophagy inhibitors or suppressing autophagy promoting genes, motor symptoms and motor neuron death are accelerated. Conversely stimulation of autophagy alleviates motor neuron degeneration.Therefore, autophagy represents an important target when developing novel treatments in ALS.
38 citations
01 Jan 2007
TL;DR: It is hypothesized that, following slight insults, both UP and autophagy are induced; if toxic stimuli are prolonged, these pathways are overwhelmed and cell death occurs.
33 citations
Cited by
More filters
TL;DR: An overview of the role of autophagy in neurodegenerative disease is provided, focusing particularly on less frequently considered lysosomal clearance mechanisms and their considerable impact on disease.
Abstract: This Review provides an overview of the role of autophagy, a key lysosomal degradative process, in neurodegenerative diseases. The study of various neurodegenerative diseases has shown that defects in autophagy can arise at different points in the pathway, and this has implications for the successful modulation of autophagy for therapeutic purposes. The Review also discusses the latest developments in targeting alterations in autophagy as a therapeutic strategy for neurodegenerative diseases.
1,643 citations
TL;DR: In this article, the authors focus on the neuronal population associated with the motor symptoms of Parkinson's disease, the dopaminergic neurons of the substantia nigra, and try to understand how ageing puts these neurons at risk to the extent that a slight change in protein metabolism or mitochondrial function can push the cells over the edge leading to catastrophic cell death.
663 citations
TL;DR: It is suggested that progerin-induced aging can be used to reveal late-onset age-related disease features in hiPSC-based disease models.
597 citations
TL;DR: The accumulated evidence indicates that multiple events converge to mediate METH-induced terminal degeneration and neuronal apoptosis, and suggest that pharmacological strategies geared towards the prevention and treatment of the deleterious effects of this drug will need to attack the various pathways that form the substrates of METH toxicity.
553 citations
TL;DR: Continuous low-level exposure of mice to MPTP causes a Parkinson-like syndrome in an alpha-synuclein-dependent manner, and the inhibition of the ubiquitinproteasome system and the production of inclusion bodies were reduced.
Abstract: In animals, sporadic injections of the mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively damage dopaminergic neurons but do not fully reproduce the features of human Parkinson's disease. We have now developed a mouse Parkinson's disease model that is based on continuous MPTP administration with an osmotic minipump and mimics many features of the human disease. Although both sporadic and continuous MPTP administration led to severe striatal dopamine depletion and nigral cell loss, we find that only continuous administration of MPTP produced progressive behavioral changes and triggered formation of nigral inclusions immunoreactive for ubiquitin and α-synuclein. Moreover, only continuous MPTP infusions caused long-lasting activation of glucose uptake and inhibition of the ubiquitin-proteasome system. In mice lacking α-synuclein, continuous MPTP delivery still induced metabolic activation, but induction of behavioral symptoms and neuronal cell death were almost completely alleviated. Furthermore, the inhibition of the ubiquitinproteasome system and the production of inclusion bodies were reduced. These data suggest that continuous low-level exposure of mice to MPTP causes a Parkinson-like syndrome in an α-synuclein-dependent manner.
511 citations