Upregulation of a small vault RNA (svtRNA2-1a) is an early event in Parkinson disease and induces neuronal dysfunction

Elena Miñones-Moyano; Marc R. Friedländer; Joan Pallares; Birgit Kagerbauer; Sílvia Porta; Georgia Escaramís; Isidre Ferrer; Xavier Estivill; Eulàlia Martí

doi:10.4161/rna.24813

Upregulation of a small vault RNA (svtRNA2-1a) is an early event in Parkinson disease and induces neuronal dysfunction

RNA Biology ◽

10.4161/rna.24813 ◽

2013 ◽

Vol 10 (7) ◽

pp. 1093-1106 ◽

Cited By ~ 22

Author(s):

Elena Miñones-Moyano ◽

Marc R. Friedländer ◽

Joan Pallares ◽

Birgit Kagerbauer ◽

Sílvia Porta ◽

...

Keyword(s):

Parkinson Disease ◽

Early Event ◽

Neuronal Dysfunction ◽

Vault Rna

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Increased Intestinal Permeability and Parkinson Disease Patients: Chicken or Egg?

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100013202 ◽

2012 ◽

Vol 39 (2) ◽

pp. 185-188 ◽

Cited By ~ 35

Author(s):

D. Salat-Foix ◽

K. Tran ◽

R. Ranawaya ◽

J. Meddings ◽

O. Suchowersky

Keyword(s):

Parkinson Disease ◽

Intestinal Permeability ◽

Sucrose Concentration ◽

Significant Proportion ◽

Gastrointestinal Symptoms ◽

Early Event ◽

Abnormal Result ◽

Non Invasive ◽

Invasive Test ◽

Gastrointestinal Permeability

Gastrointestinal involvement is a frequent and early event in the course of Parkinson Disease (PD), and may have a prominent role in the early pathophysiology of the disease. On the other hand, derangement in intestinal permeability could also result from the involvement of the gastrointestinal tract over the course of the disease.Patients and methods:The intestinal permeability of 12 non-selected PD patients was studied using a validated, non-invasive test; these results were compared to predefined age-adjusted reference values.Results:4/12 PD patients had abnormal gastrointestinal permeability; two had both an abnormal lactulose/mannitol ratio and an abnormal sucrose concentration, and two an isolated abnormal result. An increased lactulose/mannitol ratio is consistent with defect of either the enterocytes or the tight junctions between them.Conclusion:Intestinal permeability is increased in a significant proportion of unselected PD patients with minimal gastrointestinal symptoms. The significance of this finding needs to be further evaluated.

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Efficient propagation of misfolded tau between individual neurons occurs in absence of degeneration

10.1101/372029 ◽

2018 ◽

Author(s):

Grace I Hallinan ◽

Mariana Vargas-Caballero ◽

Jonathan West ◽

Katrin Deinhardt

Keyword(s):

Cell Death ◽

Axonal Transport ◽

Tau Protein ◽

Neuronal Death ◽

Early Event ◽

Neuronal Dysfunction ◽

Tau Pathology ◽

Functional Consequences ◽

Tau Aggregation ◽

The Brain

AbstractIn Alzheimer’s disease, misfolded tau protein propagates through the brain in a prion-like manner along connected circuits. Tauopathy correlates with significant neuronal death, but the links between tau aggregation, propagation, neuronal dysfunction and death remain poorly understood, and the direct functional consequences for the neuron containing the tau aggregates are unclear. Here, by monitoring individual neurons within a minimal circuit, we demonstrate that misfolded tau efficiently spreads from presynaptic to postsynaptic neurons. Within postsynaptic cells, tau aggregates initially in distal axons, while proximal axons remain free of tau pathology. In the presence of tau aggregates neurons display axonal transport deficits, but remain viable and electrically competent. This shows that misfolded tau species are not immediately toxic to neurons, and suggests that propagation of misfolded tau is an early event in disease, occurring prior to neuronal dysfunction and cell death.

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