Publications by authors named "P Riederer"

802 Publications

Iron as the concert master in the pathogenic orchestra playing in sporadic Parkinson's disease.

J Neural Transm (Vienna) 2021 Oct 12;128(10):1577-1598. Epub 2021 Oct 12.

Department of Medical Physiology, University of Nairobi, P.O. Box 30197, Nairobi, 00100, Kenya.

About 60 years ago, the discovery of a deficiency of dopamine in the nigro-striatal system led to a variety of symptomatic therapeutic strategies to supplement dopamine and to substantially improve the quality of life of patients with Parkinson's disease (PD). Since these seminal developments, neuropathological, neurochemical, molecular biological and genetic discoveries contributed to elucidate the pathology of PD. Oxidative stress, the consequences of reactive oxidative species, reduced antioxidative capacity including loss of glutathione, excitotoxicity, mitochondrial dysfunction, proteasomal dysfunction, apoptosis, lysosomal dysfunction, autophagy, suggested to be causal for ɑ-synuclein fibril formation and aggregation and contributing to neuroinflammation and neural cell death underlying this devastating disorder. However, there are no final conclusions about the triggered pathological mechanism(s) and the follow-up of pathological dysfunctions. Nevertheless, it is a fact, that iron, a major component of oxidative reactions, as well as neuromelanin, the major intraneuronal chelator of iron, undergo an age-dependent increase. And ageing is a major risk factor for PD. Iron is significantly increased in the substantia nigra pars compacta (SNpc) of PD. Reasons for this finding include disturbances in iron-related import and export mechanisms across the blood-brain barrier (BBB), localized opening of the BBB at the nigro-striatal tract including brain vessel pathology. Whether this pathology is of primary or secondary importance is not known. We assume that there is a better fit to the top-down hypotheses and pathogens entering the brain via the olfactory system, then to the bottom-up (gut-brain) hypothesis of PD pathology. Triggers for the bottom-up, the dual-hit and the top-down pathologies include chemicals, viruses and bacteria. If so, hepcidin, a regulator of iron absorption and its distribution into tissues, is suggested to play a major role in the pathogenesis of iron dyshomeostasis and risk for initiating and progressing ɑ-synuclein pathology. The role of glial components to the pathology of PD is still unknown. However, the dramatic loss of glutathione (GSH), which is mainly synthesized in glia, suggests dysfunction of this process, or GSH uptake into neurons. Loss of GSH and increase in SNpc iron concentration have been suggested to be early, may be even pre-symptomatic processes in the pathology of PD, despite the fact that they are progression factors. The role of glial ferritin isoforms has not been studied so far in detail in human post-mortem brain tissue and a close insight into their role in PD is called upon. In conclusion, "iron" is a major player in the pathology of PD. Selective chelation of excess iron at the site of the substantia nigra, where a dysfunction of the BBB is suggested, with peripherally acting iron chelators is suggested to contribute to the portfolio and therapeutic armamentarium of anti-Parkinson medications.
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http://dx.doi.org/10.1007/s00702-021-02414-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507512PMC
October 2021

Is Galactose a Hormetic Sugar? An Exploratory Study of the Rat Hippocampal Redox Regulatory Network.

Mol Nutr Food Res 2021 Aug 27:e2100400. Epub 2021 Aug 27.

Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.

Scope: Galactose, a ubiquitous monosaccharide with incompletely understood physiology is often exploited for inducing oxidative-stress mediated aging in animals. Recent research demonstrates that galactose can conserve cellular function during periods of starvation and prevent/alleviate cognitive deficits in a rat model of sporadic Alzheimer's disease. The present aim is to examine the acute effects of oral galactose on the redox regulatory network (RRN).

Methods And Results: Rat plasma and hippocampal RRNs are analyzed upon acute orogastric gavage of galactose (200 mg kg ). No systemic RRN disbalance is observed; however, a mild pro-oxidative shift accompanied by a paradoxical increment in tissue reductive capacity suggesting overcompensation of endogenous antioxidant systems is observed in the hippocampus. Galactose-induced increment of reductive capacity is accompanied by inflation of the hippocampal pool of nicotinamide adenine dinucleotide phosphates indicating ROS detoxification through disinhibition of the oxidative pentose phosphate pathway flux, reduced neuronal activity, and upregulation of Leloir pathway gatekeeper enzyme galactokinase-1.

Conclusion: Based on the observed findings, and in the context of previous work on galactose, a hormetic hypothesis of galactose is proposed suggesting that the protective effects may be inseparable from its pro-oxidative action at the biochemical level.
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http://dx.doi.org/10.1002/mnfr.202100400DOI Listing
August 2021

No Metagenomic Evidence of Causative Viral Pathogens in Postencephalitic Parkinsonism Following Encephalitis Lethargica.

Microorganisms 2021 Aug 12;9(8). Epub 2021 Aug 12.

Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

Postencephalitic parkinsonism (PEP) is a disease of unknown etiology and pathophysiology following encephalitis lethargica (EL), an acute-onset polioencephalitis of cryptic cause in the 1920s. PEP is a tauopathy with multisystem neuronal loss and gliosis, clinically characterized by bradykinesia, rigidity, rest tremor, and oculogyric crises. Though a viral cause of EL is likely, past polymerase chain reaction-based investigations in the etiology of both PEP and EL were negative. PEP might be caused directly by an unknown viral pathogen or the consequence of a post-infectious immunopathology. The development of metagenomic next-generation sequencing in conjunction with bioinformatic techniques has generated a broad-range tool for the detection of unknown pathogens in the recent past. Retrospective identification and characterization of pathogens responsible for past infectious diseases can be successfully performed with formalin-fixed paraffin-embedded (FFPE) tissue samples. In this study, we analyzed 24 FFPE brain samples from six patients with PEP by unbiased metagenomic next-generation sequencing. Our results show that no evidence for the presence of a specific or putative (novel) viral pathogen was found, suggesting a likely post-infectious immune-mediated etiology of PEP.
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http://dx.doi.org/10.3390/microorganisms9081716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398509PMC
August 2021

Kurt Jellinger, Doyen of international neuropathology.

J Neural Transm (Vienna) 2021 Oct 22;128(10):1479-1480. Epub 2021 Aug 22.

Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Margarete Hoeppel-Platz 1, 97080, Wuerzburg, Germany.

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http://dx.doi.org/10.1007/s00702-021-02397-xDOI Listing
October 2021

Correction to: Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses.

J Neural Transm (Vienna) 2021 Jun 19. Epub 2021 Jun 19.

Institut für Virologie und Immunbiologie, Universität Würzburg, Versbacherstraße Straße 7, 97078, Würzburg, Germany.

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http://dx.doi.org/10.1007/s00702-021-02356-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214065PMC
June 2021
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