scholarly journals ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability

2020 ◽  
Author(s):  
Nazmiye Özkan ◽  
Max Koppers ◽  
Inge van Soest ◽  
Alexandra van Harten ◽  
Nalan Liv ◽  
...  
Keyword(s):  
Neuronal Function ◽  
Organelle Communication

ABSTRACTNeuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the ER and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.

scholarly journals ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nazmiye Özkan ◽  
Max Koppers ◽  
Inge van Soest ◽  
Alexandra van Harten ◽  
Daphne Jurriens ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Neuronal Function ◽  
Organelle Communication

AbstractNeuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.

Deletion of 12/15-Lipoxygenase Preserves Retinal Neuronal Function in Diabetic Retinopathy

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 34-LB
Author(s):  
MING WAN ◽  
AHMED IBRAHIM ◽  
MOHAMED EL-SHAFEY ◽  
KHALED ELMASRY ◽  
SAMER ABDULMONEIM ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Neuronal Function

Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
Author(s):  
Jozef Hanes ◽  
Eva Dobakova ◽  
Petra Majerova
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neurodegenerative Disorders ◽  
Brain Barrier ◽  
Neuronal Function ◽  
Brain Drug Delivery ◽  
Naturally Occurring ◽  
Blood Brain ◽  
Traditional Approaches ◽  
The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

scholarly journals Deubiquitylating enzymes in neuronal health and disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fatima Amer-Sarsour ◽  
Alina Kordonsky ◽  
Yevgeny Berdichevsky ◽  
Gali Prag ◽  
Avraham Ashkenazi
Keyword(s):  
Human Brain ◽  
Neurodegenerative Disorders ◽  
Structure And Function ◽  
Pivotal Role ◽  
Protein Homeostasis ◽  
Neuronal Function ◽  
Health And Disease ◽  
And Function

AbstractUbiquitylation and deubiquitylation play a pivotal role in protein homeostasis (proteostasis). Proteostasis shapes the proteome landscape in the human brain and its impairment is linked to neurodevelopmental and neurodegenerative disorders. Here we discuss the emerging roles of deubiquitylating enzymes in neuronal function and survival. We provide an updated perspective on the genetics, physiology, structure, and function of deubiquitylases in neuronal health and disease.

scholarly journals Ndufs4 ablation decreases synaptophysin expression in hippocampus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Subrata Kumar Shil ◽  
Yoshiteru Kagawa ◽  
Banlanjo Abdulaziz Umaru ◽  
Fumika Nanto-Hara ◽  
Hirofumi Miyazaki ◽  
...  
Keyword(s):  
Nadh Dehydrogenase ◽  
Leigh Syndrome ◽  
Mitochondrial Respiratory Chain ◽  
Mitochondrial Activity ◽  
Mitochondrial Complex ◽  
Neuronal Function ◽  
Mouse Hippocampus ◽  
Extracellular Regulated Kinase ◽  
Presynaptic Protein

AbstractAltered function of mitochondrial respiratory chain in brain cells is related to many neurodegenerative diseases. NADH Dehydrogenase (Ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and its mutation in human is associated with Leigh syndrome. However, the molecular biological role of Ndufs4 in neuronal function is poorly understood. In this study, upon Ndufs4 expression confirmation in NeuN-positive neurons, and GFAP-positive astrocytes in WT mouse hippocampus, we found significant decrease of mitochondrial respiration in Ndufs4-KO mouse hippocampus. Although there was no change in the number of NeuN positive neurons in Ndufs4-KO hippocampus, the expression of synaptophysin, a presynaptic protein, was significantly decreased. To investigate the detailed mechanism, we silenced Ndufs4 in Neuro-2a cells and we observed shorter neurite lengths with decreased expression of synaptophysin. Furthermore, western blot analysis for phosphorylated extracellular regulated kinase (pERK) revealed that Ndufs4 silencing decreases the activity of ERK signalling. These results suggest that Ndufs4-modulated mitochondrial activity may be involved in neuroplasticity via regulating synaptophysin expression.

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