Publications by Patrick Aebischer

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Targeting mitophagy to activate the recycling of faulty mitochondria during aging is a strategy to mitigate muscle decline. We present results from a randomized, placebo-controlled trial in middle-aged adults where we administer a postbiotic compound Uroli ...

Neurotrophic factors which act on motor neurons may provide an efficient treatment for amyotrophic lateral sclerosis. In order to overcome the difficulty of administering proteins into the central nervous system, it is possible to use a gene therapy approa ...

Allogeneic MHC-incompatible organ or cell grafts are usually promptly rejected by immunocompetent hosts. Here we tested allogeneic beta-islet cell graft acceptance by immune or naive C57BL/6 mice rendered diabetic with streptozotocin (STZ). Fully MHC-misma ...

The controlled delivery of antibodies by immunoisolated bioimplants containing genetically engineered cells is an attractive and safe approach for chronic treatments. To reach therapeutic antibody levels there is a need to generate renewable cell lines, wh ...

One of the core pathological features of Alzheimer's disease (AD) is the accumulation of amyloid plaques in the brain. Current efforts of medical imaging research aim at visualizing amyloid plaques in living patients in order to evaluate the progression of ...

To determine whether neurturin (NTN), a recently identified homologue of glial cell line-derived neurotrophic factor (GDNF), is able to preserve tyrosine hydroxylase immunoreactivity (TH-IR) in a rat model of Parkinson's disease, polymer encapsulated cells ...

The G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene is the most common genetic cause of Parkinson's disease (PD), accounting for a significant proportion of both autosomal dominant familial and sporadic PD cases. Our aim in the present study is to generate a mammalian model of mutant G2019S LRRK2 pathogenesis, which reproduces the robust nigral neurodegeneration characteristic of PD. We developed adenoviral vectors to drive neuron-specific expression of full-length wild-type or mutant G2019

Numerous studies have shown the neuroprotective and regenerative benefits of glial cell line-derived neurotrophic factor (GDNF) in animal models of PD. Brain delivery of GDNF can, however, be associated with limiting side-effects in both primates and PD pa ...

Loss of function of parkin, an ubiquitin ligase, is responsible for autosomal recessive juvenile parkinsonism (AR-JP). Parkin-associated endothelin receptor-like receptor (Pael-R) was identified as an authentic substrate of parkin and is thought to accumul ...

Phosphorylation is involved in numerous neurodegenerative diseases. In particular, alpha-synuclein is extensively phosphorylated in aggregates in patients suffering from synucleinopathies. However, the share of this modification in the events that lead to ...

Growing neurites are guided through their environment during development and regeneration via different cellular and extracellular matrix (ECM) molecular cues. To mimic cell-matrix interactions, a three-dimensional (3D) hydrogel-based ECM equivalent contai ...

Alzheimer's disease is the most prevalent tauopathy and cause of dementia. We investigate the hypothesis that reactivation of plasticity can restore function in the presence of neuronal damage resulting from tauopathy. We investigated two models with tau h ...

PURPOSE: Intraventricular cellular delivery of adenosine was recently shown to be transiently efficient in the suppression of seizure activity in the rat kindling model of epilepsy. We tested whether the suppression of seizures by adenosine-releasing graft ...

The involvement of alpha-synuclein in familial forms of Parkinson's disease suggests a potential causative role in the pathogenesis. We have explored the possibility of generating animal models of Parkinson's disease by overexpressing alpha-synuclein in the nigrostriatal pathway using viral vectors. Both lentiviral and adeno-associated vectors efficiently transduce dopaminergic neurons in the substantia nigra, and transgenic expression of alpha-synuclein leads to the progressive loss of neurons positive for

We explored the relationship between ubiquitin proteasome system (UPS) and lysosomal markers and the formation of alpha-synuclein (alpha-syn) inclusions in nigral neurons in Parkinson disease (PD). Lysosome Associated Membrane Protein 1(LAMP1), Cathepsin D ...

The ability to organize cells in three dimensions (3D) is an important component of tissue engineering. This study sought to develop an extracellular matrix (ECM) equivalent with a physicochemical structure capable of supporting neurite extension from prim ...

Recombinant adeno-associated viral (AAV) vectors of serotypes 6, 8, and 9 were characterized as tools for gene delivery to dopaminergic neurons in the substantia nigra for future gene therapeutic applications in Parkinson's disease. While vectors of all th ...

Human neural progenitor cells (hNPC) hold great potential as an ex vivo system for delivery of therapeutic proteins to the central nervous system. When cultured as aggregates, termed neurospheres, hNPC are capable of significant in vitro expansion. In the ...

An increase in α-synuclein levels due to gene duplications/triplications or impaired degradation is sufficient to trigger its aggregation and cause familial Parkinson disease (PD). Therefore, lowering α-synuclein levels represents a viable therapeutic strategy for the treatment of PD and related synucleinopathies. Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances α-synuclein autophagic degradation in a kinas

Patrick Aebischer

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Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Treatment of amyotrophic lateral sclerosis using a gene therapy approach

Allogeneic beta-islet cells correct diabetes and resist immune rejection

Genetic engineering of cell lines using lentiviral vectors to achieve antibody secretion following encapsulated implantation

Imaging brain amyloid deposition using grating-based differential phase contrast tomography

Neurturin protects dopaminergic neurons following medial forebrain bundle axotomy

Encapsulated neural transplants

A Rat Model of Progressive Nigral Neurodegeneration Induced by the Parkinson's Disease-Associated G2019S Mutation in LRRK2

Transient striatal delivery of GDNF via encapsulated cells leads to sustained behavioral improvement in a bilateral model of Parkinson disease

Targeted overexpression of the parkin substrate Pael-R in the nigrostriatal system of adult rats to model Parkinson's disease

Phosphorylation does not prompt, nor prevent, the formation of alpha-synuclein toxic species in a rat model of Parkinson's disease

Three-dimensional extracellular matrix engineering in the nervous system

Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology

Seizure suppression by adenosine-releasing cells is independent of seizure frequency

Viral vectors, animal models and new therapies for Parkinson's disease

Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions

Hydrogel-based three-dimensional matrix for neural cells

Direct and Retrograde Transduction of Nigral Neurons with AAV6, 8, and 9 and Intraneuronal Persistence of Viral Particles

Lentiviral vector-mediated genetic modification of human neural progenitor cells for ex vivo gene therapy

Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo