Lentiviral nigral delivery of GDNF does not prevent neurodegeneration in a genetic rat model of Parkinson's disease

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Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation

Sandrine Gerber, Céline Marie Anne Journot, Laura Camille Louise Nicolle

There is an increasing interest in cationic polymers as important constituents of non-viral gene delivery vectors. In the present study, we developed a versatile synthetic route for the production of covalent polymeric conjugates consisting of water-solubl ...

2021

Reverse engineering Lewy bodies: how far have we come and how far can we go?

Hilal Lashuel, Somanath Jagannath, Mohamed Bilal Fares

Lewy bodies (LBs) are α-synuclein (α-syn)-rich intracellular inclusions that are an important pathological hallmark of Parkinson disease and several other neurodegenerative diseases. Increasing evidence suggests that the aggregation of α-syn has a central ...

2021

Parkinson mice show functional and molecular changes in the gut long before motoric disease onset

Hilal Lashuel

Background: There is increasing evidence that Parkinson's disease (PD) might start in the gut, thus involving and compromising also the enteric nervous system (ENS). At the clinical onset of the disease the majority of dopaminergic neurons in the midbrain ...

2021

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration

Hilal Lashuel, Sonia Donzelli

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteost ...

2021

Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease

Hilal Lashuel

With the advent of the genetic era in Parkinson's disease (PD) research in 1997, alpha-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an econom ...

NATURE RESEARCH2021

Late post‐natal neurometabolic development in healthy male rats using 1 H and 31 P Magnetic Resonance Spectroscopy

Rolf Gruetter, Cristina Ramona Cudalbu Moldovan, Veronika Rackayová, Guillaume Donati, Dunja Simicic

Brain metabolism evolves rapidly during early post‐natal development in the rat. While changes in amino acids, energy metabolites, antioxidants or metabolites involved in phospholipid metabolism have been reported in the early stages, neurometabolic change ...

2021

A new rat model of creatine transporter deficiency reveals behavioral disorder and altered brain metabolism

Hirotaka Yamada, Maria del Carmen Sandi Perez, Cristina Ramona Cudalbu Moldovan, Dunja Simicic, Jocelin Grosse

Creatine is an organic compound used as fast phosphate energy buffer to recycle ATP, important in tissues with high energy demand such as muscle or brain. Creatine is taken from the diet or endogenously synthetized by the enzymes AGAT and GAMT, and specifi ...

Nature Research2021

Cell Type-Specific Membrane Potential Changes in Dorsolateral Striatum Accompanying Reward-Based Sensorimotor Learning

Tanya C Sippy, Carl Petersen, Sylvain Crochet

The striatum integrates sensorimotor and motivational signals, likely playing a key role in reward-based learning of goal-directed behavior. However, cell type-specific mechanisms underlying reinforcement learning remain to be precisely determined. Here, w ...

OXFORD UNIV PRESS2021

Structural architecture of the Neuronal-Glial-Vascular system

Eleftherios Zisis

Brain functionality relies on the neuronal-glial-vascular (NGV) ensemble for energy support. However, the details of the complex biological mechanisms involved in these processes and the microscopic interactions between these three components are not yet f ...

EPFL2021

Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity

Xi Chen, Elpida Tsika

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of late-onset, autosomal-dominant familial Parkinson's disease (PD). LRRK2 functions as both a kinase and GTPase, and PD-linked mutations are known to influence both enzymatic acti ...

National Academy of Sciences2020

The effect of the functional interaction between PGC-1α and Parkin on mitochondrial quality control in Parkinson's disease

Lu Zheng

Although several genetic factors have been directly associated to Parkinsonâ s disease (PD), no single pathway has emerged to explain the etiology of this neurodegenerative disease. To further understand the cause of Parkinsonâ s disease (PD), it is ther ...

EPFL2016

Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry

Patrick Aebischer, Nicole Déglon, Diana Zala, Valérie Gafner

Gene expression changes are a hallmark of the neuropathology of Huntington's disease (HD), but the exact molecular mechanisms of this effect remain uncertain. Here, we report that in vitro models of disease comprised of primary striatal neurons expressing ...

2008