Autophagy
autophagy
‘Autophagy regulates neurotransmission by controlling the axonal endoplasmic reticulum’
How does a neuron decide when and where to make a synapse?
Precise synaptic connectivity is a prerequisite for the function of neural circuits, yet individual neurons, taken out of their developmental context, readily form unspecific synapses. How does genetically encoded brain wiring deal with this apparent contradiction? Brain wiring is a developmental growth process that is not only characterized by precision, but also flexibility and robustness. As in any other growth process, cellular interactions are restricted in space and time. Correspondingly, molecular and cellular interactions are restricted to those that 'get to see' each other during development. This seminar will explore the question how neurons decide when and where to make synapses using the Drosophila visual system as a model. New findings reveal that pattern formation during growth and the kinetics of live neuronal interactions restrict synapse formation and partner choice for neurons that are not otherwise prevented from making incorrect synapses in this system. For example, cell biological mechanisms like autophagy as well as developmental temperature restrict inappropriate partner choice through a process of kinetic exclusion that critically contributes to wiring specificity. The seminar will explore these and other neuronal strategies when and where to make synapses during developmental growth that contribute to precise, flexible and robust outcomes in brain wiring.
Neuronal autophagy promotes the hormonal regulation of brain cognitive and metabolic functions
Targeting selective autophagy against neurodegenerative diseases
Protein quality control is essential for maintenance of a healthy and functional proteome that can attend the multiplicity of cellular functions. Failure of the systems that contribute to protein homeostasis, the so called proteostasis networks, have been identified in the pathogenesis of multiple neurodegenerative disorders and demonstrated to contribute to disease onset and progression. We are interested in autophagy, one of the components of the proteostasis network, and in the interplay of wo selective types of autophagy, chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI), with neurodegeneration. We have recently found that pathogenic proteins involved in common neurodegenerative conditions such as tauopathies or Parkinson’s disease, can exert a toxic effect in both types of selective types of autophagy compromising their functioning. We have now used mouse models with compromised CMA that support increased propagation of proteins such as tau and alpha-synuclein and an exacerbation of disease phenotype with aging. Conversely, genetic or chemical upregulation of CMA in this context of proteotoxicity slow down disease progression by facilitating effective intracellular removal of pathogenic proteins. Our findings highlight CMA and eMI as potential novel therapeutic targets against neurodegeneration.
Activation of non-nuclear estrogen receptor signaling pathways with PaPE-1 as a potential remedy for amyloid-beta induced toxicity: Impact on autophagy
FENS Forum 2024
Altered autophagy in KANSL1 haploinsufficient iPSC-derived astrocytes
FENS Forum 2024
Autophagy modulation of glial neuroinflammatory responses in Parkinson’s disease
FENS Forum 2024
Autophagy regulation during brain development and synaptogenesis
FENS Forum 2024
Chaperone mediated autophagy is deficient in spinal motoneurons of ALS patients
FENS Forum 2024
Dissecting the role of autophagy to elucidate the differential response of oligodendrocytes and astrocytes to hypoxic injury in vitro
FENS Forum 2024
Effect of melatonin on the autophagy in the prefrontal cortex of streptozotocin-induced type 1 diabetic rats
FENS Forum 2024
Infantile ceroid neuro-lipofuscinosis: Linking autophagy, altered chloride homeostasis, and enhanced brain excitability
FENS Forum 2024
Identification of sex-specific autophagy enhancers for dementia
FENS Forum 2024
Impaired macroautophagy in oligodendrocyte precursor cells exacerbates aging-related cognitive deficits via a senescence-associated signaling
FENS Forum 2024
Interplay between tubulin tyrosination, autophagy and neuron health
FENS Forum 2024
Longitudinal autophagy profiling of mammalian brain circuits reveals dynamic and sustained mitophagy throughout healthy aging
FENS Forum 2024
Neuroprotective effect of bicifadine, sertraline, and tiagabine with autophagy-inducing activity in 6-hydroxydopamine Parkinson’s models
FENS Forum 2024
A novel role for autophagy protein WIPI2 in cognitive fitness
FENS Forum 2024
Pharmacological stimulation of autophagy to rescue proteinopathy and cognitive decline in lysosomal storage disorders
FENS Forum 2024
Rab5-associated transcriptome reveals a new link between endosomes and autophagy in axons
FENS Forum 2024
Role of late endosomal autophagy-dependent secretion in neurodegeneration
FENS Forum 2024
The serine-threonine kinase Ndr2 impairs spatial memory and regulates autophagy and protein expression in the synapses of the ageing hippocampus
FENS Forum 2024
Testing the therapeutic effects of autophagy enhancement in a Rett syndrome mouse model
FENS Forum 2024
TFEB-loaded exosomes mediated autophagy induction in Alzheimer’s disease
FENS Forum 2024
Tibolone improves locomotor function in a rat model of spinal cord injury by modulating apoptosis and autophagy
FENS Forum 2024