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Article ; Online: Like an Old Married Couple.

Neutzner, Albert

Journal of pediatric ophthalmology and strabismus

2017 Volume 54, Issue 6, Page(s) 334–336

MeSH term(s)	Biomedical Research ; Eye Diseases/diagnosis ; Eye Diseases/genetics ; Eye Diseases/metabolism ; Genetic Testing ; Humans ; Mitochondria/metabolism
Language	English
Publishing date	2017-11-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	800921-1
ISSN	1938-2405 ; 0191-3913
ISSN (online)	1938-2405
ISSN	0191-3913
DOI	10.3928/01913913-20170918-01
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Article: Outer mitochondrial membrane E3 Ub ligase MARCH5 controls mitochondrial steps in peroxisome biogenesis.

Verhoeven, Nicolas / Oshima, Yumiko / Cartier, Etienne / Neutzner, Albert / Boyman, Liron / Karbowski, Mariusz

bioRxiv : the preprint server for biology

2023

Abstract: Peroxisome : Summary: The authors found that mitochondrial E3 Ub ligase MARCH5 controls the formation of mitochondria-derived pre-peroxisomes. The data support the hybrid, mitochondria-dependent model of peroxisome biogenesis and reveal that MARCH5 is ...

Abstract	Peroxisome Summary: The authors found that mitochondrial E3 Ub ligase MARCH5 controls the formation of mitochondria-derived pre-peroxisomes. The data support the hybrid, mitochondria-dependent model of peroxisome biogenesis and reveal that MARCH5 is an essential mitochondrial protein in this process.
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.31.555756
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Article ; Online: Impact of aging on meningeal gene expression.

Neutzner, Melanie / Kohler, Corina / Frank, Stephan / Killer, Hanspeter E / Neutzner, Albert

Fluids and barriers of the CNS

2023 Volume 20, Issue 1, Page(s) 12

Abstract: Background: The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic system essential for maintaining fluid dynamics inside the cerebrospinal ... ...

Abstract	Background: The three-layered meninges cover and protect the central nervous system and form the interface between cerebrospinal fluid and the brain. They are host to a lymphatic system essential for maintaining fluid dynamics inside the cerebrospinal fluid-filled subarachnoid space and across the brain parenchyma via their connection to glymphatic structures. Meningeal fibroblasts lining and traversing the subarachnoid space have direct impact on the composition of the cerebrospinal fluid through endocytotic uptake as well as extensive protein secretion. In addition, the meninges are an active site for immunological processes and act as gatekeeper for immune cells entering the brain. During aging in mice, lymphatic drainage from the brain is less efficient contributing to neurodegenerative processes. Aging also affects the immunological status of the meninges, with increasing numbers of T cells, changing B cell make-up, and altered macrophage complement. Methods: We employed RNASeq to measure gene expression and to identify differentially expressed genes in meninges isolated from young and aged mice. Using Ingenuity pathway, GO term, and MeSH analyses, we identified regulatory pathways and cellular functions in meninges affected by aging. Results: Aging had profound impact on meningeal gene expression. Pathways related to innate as well as adaptive immunity were affected. We found evidence for increasing numbers of T and B lymphocytes and altered activity profiles for macrophages and other myeloid cells. Furthermore, expression of pro-inflammatory cytokine and chemokine genes increased with aging. Similarly, the complement system seemed to be more active in meninges of aged mice. Altered expression of solute carrier genes pointed to age-dependent changes in cerebrospinal fluid composition. In addition, gene expression for secreted proteins showed age-dependent changes, in particular, genes related to extracellular matrix composition and organization were affected. Conclusions: Aging has profound effects on meningeal gene expression; thereby affecting the multifaceted functions meninges perform to maintain the homeostasis of the central nervous system. Thus, age-dependent neurodegenerative processes and cognitive decline are potentially in part driven by altered meningeal function.
MeSH term(s)	Mice ; Animals ; Meninges/metabolism ; Central Nervous System ; Brain/physiology ; Aging ; Gene Expression
Language	English
Publishing date	2023-02-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2595406-4
ISSN	2045-8118 ; 2045-8118
ISSN (online)	2045-8118
ISSN	2045-8118
DOI	10.1186/s12987-023-00412-9
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Article ; Online: Large-scale in-silico analysis of CSF dynamics within the subarachnoid space of the optic nerve.

Rossinelli, Diego / Fourestey, Gilles / Killer, Hanspeter Esriel / Neutzner, Albert / Iaccarino, Gianluca / Remonda, Luca / Berberat, Jatta

Fluids and barriers of the CNS

2024 Volume 21, Issue 1, Page(s) 20

Abstract: Background: Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer's and Parkinson's disease, as well as frontotemporal ... ...

Abstract	Background: Impaired cerebrospinal fluid (CSF) dynamics is involved in the pathophysiology of neurodegenerative diseases of the central nervous system and the optic nerve (ON), including Alzheimer's and Parkinson's disease, as well as frontotemporal dementia. The smallness and intricate architecture of the optic nerve subarachnoid space (ONSAS) hamper accurate measurements of CSF dynamics in this space, and effects of geometrical changes due to pathophysiological processes remain unclear. The aim of this study is to investigate CSF dynamics and its response to structural alterations of the ONSAS, from first principles, with supercomputers. Methods: Large-scale in-silico investigations were performed by means of computational fluid dynamics (CFD) analysis. High-order direct numerical simulations (DNS) have been carried out on ONSAS geometry at a resolution of 1.625 μm/pixel. Morphological changes on the ONSAS microstructure have been examined in relation to CSF pressure gradient (CSFPG) and wall strain rate, a quantitative proxy for mass transfer of solutes. Results: A physiological flow speed of 0.5 mm/s is achieved by imposing a hydrostatic pressure gradient of 0.37-0.67 Pa/mm across the ONSAS structure. At constant volumetric rate, the relationship between pressure gradient and CSF-accessible volume is well captured by an exponential curve. The ONSAS microstructure exhibits superior mass transfer compared to other geometrical shapes considered. An ONSAS featuring no microstructure displays a threefold smaller surface area, and a 17-fold decrease in mass transfer rate. Moreover, ONSAS trabeculae seem key players in mass transfer. Conclusions: The present analysis suggests that a pressure drop of 0.1-0.2 mmHg over 4 cm is sufficient to steadily drive CSF through the entire subarachnoid space. Despite low hydraulic resistance, great heterogeneity in flow speeds puts certain areas of the ONSAS at risk of stagnation. Alterations of the ONSAS architecture aimed at mimicking pathological conditions highlight direct relationships between CSF volume and drainage capability. Compared to the morphological manipulations considered herein, the original ONSAS architecture seems optimized towards providing maximum mass transfer across a wide range of pressure gradients and volumetric rates, with emphasis on trabecular structures. This might shed light on pathophysiological processes leading to damage associated with insufficient CSF flow in patients with optic nerve compartment syndrome.
MeSH term(s)	Humans ; Hydrodynamics ; Intraocular Pressure ; Optic Nerve/pathology ; Optic Nerve/physiology ; Subarachnoid Space/physiology ; Cerebrospinal Fluid Pressure/physiology ; Cerebrospinal Fluid/physiology
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2595406-4
ISSN	2045-8118 ; 2045-8118
ISSN (online)	2045-8118
ISSN	2045-8118
DOI	10.1186/s12987-024-00518-8
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Article ; Online: Dysregulated Interorganellar Crosstalk of Mitochondria in the Pathogenesis of Parkinson's Disease.

Sironi, Lara / Restelli, Lisa Michelle / Tolnay, Markus / Neutzner, Albert / Frank, Stephan

Cells

2020 Volume 9, Issue 1

Abstract: The pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder, is complex and involves the impairment of crucial intracellular physiological processes. Importantly, in addition to abnormal α-synuclein aggregation, the ... ...

Abstract	The pathogenesis of Parkinson's disease (PD), the second most common neurodegenerative disorder, is complex and involves the impairment of crucial intracellular physiological processes. Importantly, in addition to abnormal α-synuclein aggregation, the dysfunction of various mitochondria-dependent processes has been prominently implicated in PD pathogenesis. Besides the long-known loss of the organelles' bioenergetics function resulting in diminished ATP synthesis, more recent studies in the field have increasingly focused on compromised mitochondrial quality control as well as impaired biochemical processes specifically localized to ER-mitochondria interfaces (such as lipid biosynthesis and calcium homeostasis). In this review, we will discuss how dysregulated mitochondrial crosstalk with other organelles contributes to PD pathogenesis.
MeSH term(s)	Endoplasmic Reticulum/genetics ; Endoplasmic Reticulum/metabolism ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism ; Lysosomes/metabolism ; Lysosomes/ultrastructure ; Mitochondria/enzymology ; Mitochondria/genetics ; Mitochondria/metabolism ; Parkinson Disease/enzymology ; Parkinson Disease/etiology ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Protein Deglycase DJ-1/genetics ; Protein Deglycase DJ-1/metabolism ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Proton-Translocating ATPases/genetics ; Proton-Translocating ATPases/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism ; alpha-Synuclein/genetics ; alpha-Synuclein/metabolism
Chemical Substances	ATP13A2 protein, human ; VPS35 protein, human ; Vesicular Transport Proteins ; alpha-Synuclein ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; parkin protein (EC 2.3.2.27) ; Protein Kinases (EC 2.7.-) ; LRRK2 protein, human (EC 2.7.11.1) ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (EC 2.7.11.1) ; PTEN-induced putative kinase (EC 2.7.11.1) ; PARK7 protein, human (EC 3.1.2.-) ; Protein Deglycase DJ-1 (EC 3.1.2.-) ; Proton-Translocating ATPases (EC 3.6.3.14)
Language	English
Publishing date	2020-01-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9010233
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Article ; Online: Large-scale morphometry of the subarachnoid space of the optic nerve.

Rossinelli, Diego / Killer, Hanspeter Esriel / Meyer, Peter / Knott, Graham / Fourestey, Gilles / Kurtcuoglu, Vartan / Kohler, Corina / Gruber, Philipp / Remonda, Luca / Neutzner, Albert / Berberat, Jatta

Fluids and barriers of the CNS

2023 Volume 20, Issue 1, Page(s) 21

Abstract: Background: The meninges, formed by dura, arachnoid and pia mater, cover the central nervous system and provide important barrier functions. Located between arachnoid and pia mater, the cerebrospinal fluid (CSF)-filled subarachnoid space (SAS) features ... ...

Abstract	Background: The meninges, formed by dura, arachnoid and pia mater, cover the central nervous system and provide important barrier functions. Located between arachnoid and pia mater, the cerebrospinal fluid (CSF)-filled subarachnoid space (SAS) features a variety of trabeculae, septae and pillars. Like the arachnoid and the pia mater, these structures are covered with leptomeningeal or meningothelial cells (MECs) that form a barrier between CSF and the parenchyma of the optic nerve (ON). MECs contribute to the CSF proteome through extensive protein secretion. In vitro, they were shown to phagocytose potentially toxic proteins, such as α-synuclein and amyloid beta, as well as apoptotic cell bodies. They therefore may contribute to CSF homeostasis in the SAS as a functional exchange surface. Determining the total area of the SAS covered by these cells that are in direct contact with CSF is thus important for estimating their potential contribution to CSF homeostasis. Methods: Using synchrotron radiation-based micro-computed tomography (SRµCT), two 0.75 mm-thick sections of a human optic nerve were acquired at a resolution of 0.325 µm/pixel, producing images of multiple terabytes capturing the geometrical details of the CSF space. Special-purpose supercomputing techniques were employed to obtain a pixel-accurate morphometric description of the trabeculae and estimate internal volume and surface area of the ON SAS. Results: In the bulbar segment, the ON SAS microstructure is shown to amplify the MECs surface area up to 4.85-fold compared to an "empty" ON SAS, while just occupying 35% of the volume. In the intraorbital segment, the microstructure occupies 35% of the volume and amplifies the ON SAS area 3.24-fold. Conclusions: We provided for the first time an estimation of the interface area between CSF and MECs. This area is of importance for estimating a potential contribution of MECs on CSF homeostasis.
MeSH term(s)	Humans ; Optic Nerve/metabolism ; Tomography, X-Ray ; Amyloid beta-Peptides/metabolism
Chemical Substances	SNCA protein, human ; Amyloid beta-Peptides
Language	English
Publishing date	2023-03-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2595406-4
ISSN	2045-8118 ; 2045-8118
ISSN (online)	2045-8118
ISSN	2045-8118
DOI	10.1186/s12987-023-00423-6
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Article: Lipocalin-type Prostaglandin D Synthase Concentration Gradients in the Cerebrospinal Fluid in Normal-tension Glaucoma Patients with Optic Nerve Sheath Compartmentation.

Pircher, Achmed / Neutzner, Albert / Montali, Margherita / Huber, Andreas / Scholl, Hendrik P N / Berberat, Jatta / Remonda, Luca / Killer, Hanspeter E

Eye and brain

2021 Volume 13, Page(s) 89–97

Abstract: Objective: To report on the lipocalin-type prostaglandin D synthase (L-PGDS) concentrations in the cerebrospinal fluid (CSF) of the perioptic and lumbar subarachnoid space (SAS) in patients with radiologically proven optic nerve (ON) sheath ... ...

Abstract	Objective: To report on the lipocalin-type prostaglandin D synthase (L-PGDS) concentrations in the cerebrospinal fluid (CSF) of the perioptic and lumbar subarachnoid space (SAS) in patients with radiologically proven optic nerve (ON) sheath compartmentation presenting as normal-tension glaucoma (NTG). Methods: Retrospective biochemical analysis of CSF in thirteen patients with ON sheath compartmentation presenting as NTG (four females, mean age 70±8 years). CSF was sampled from the SAS of the ON during ON sheath fenestration for ON sheath compartmentation and from the lumbar SAS at the time of lumbar puncture. Nephelometry was used for the quantification of L-PGDS and albumin concentration. Albumin was measured in order to assess the amount of contamination with serum in the CSF samples taken from the ON SAS. Main outcome measures were L-PGDS concentrations in the CSF of the perioptic and lumbar SAS. Results: Mean L-PGDS concentration was 24±8 mg/L in the lumbar SAS compared to 33±27 mg/L without correction of serum contamination and 45±39 mg/L after correction of serum contamination in the perioptic SAS. The difference between the lumbar and the perioptic SAS was statistically significant ( Conclusion: This study demonstrates a concentration gradient of L-PGDS levels within the CSF with a statistically significant higher concentration in the compartmentalized perioptic SAS compared to that in the lumbar SAS. Biochemical changes in the perioptic SAS might be involved in the pathophysiology in NTG patients with ON sheath compartmentation.
Language	English
Publishing date	2021-04-14
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2587460-3
ISSN	1179-2744
ISSN	1179-2744
DOI	10.2147/EB.S297274
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Article ; Online: Enzymes of ubiquitination and deubiquitination.

Neutzner, Melanie / Neutzner, Albert

Essays in biochemistry

2012 Volume 52, Page(s) 37–50

Abstract: Ubiquitination, the covalent attachment of the small protein modifier ubiquitin to a substrate protein is involved in virtually all cellular processes by mediating the regulated degradation of proteins. Aside from proteasomal degradation, ubiquitination ... ...

Abstract	Ubiquitination, the covalent attachment of the small protein modifier ubiquitin to a substrate protein is involved in virtually all cellular processes by mediating the regulated degradation of proteins. Aside from proteasomal degradation, ubiquitination plays important roles in transcriptional regulation, protein trafficking, including endocytosis and lysosomal targeting, and activation of kinases involved in signalling processes. A three-tiered enzymatic cascade consisting of E1 or ubiquitin-activating enzyme, E2 or ubiquitin-conjugating enzyme, and E3, or ubiquitin ligases, is necessary to achieve the many forms of ubiquitination known to date. In this chapter, we summarize the current knowledge on the enzymatic machinery necessary for ubiquitin activation and ligation, as well as its removal, and provide some insight into the complexity of regulatory processes governed by ubiquitination.
MeSH term(s)	Animals ; Humans ; Protein Processing, Post-Translational ; Ubiquitin/metabolism ; Ubiquitin-Activating Enzymes/metabolism ; Ubiquitin-Conjugating Enzymes/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination
Chemical Substances	Ubiquitin ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Ubiquitin-Activating Enzymes (EC 6.2.1.45)
Language	English
Publishing date	2012
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1744-1358 ; 0071-1365
ISSN (online)	1744-1358
ISSN	0071-1365
DOI	10.1042/bse0520037
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Book ; Online ; Thesis: Termination der Mitose

Neutzner, Albert

die Rolle der Phosphatase Cdc14 beim M-G1-Übergang in der Hefe Saccharomyces cerevisiae

2002

Author's details	vorgelegt von Albert Neutzner
Keywords	Abbruchreaktion ; Saccharomyces cerevisiae ; Mitose
Language	German
Size	Online-Ressource
Document type	Book ; Online ; Thesis
Thesis / German Habilitation thesis	Univ., Diss--Stuttgart, 2002
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Elevated perioptic lipocalin-type prostaglandin D synthase concentration in patients with idiopathic intracranial hypertension.

Pircher, Achmed / Montali, Margherita / Berberat, Jatta / Huber, Andreas / Miller, Neil R / Mader, Thomas H / Gibson, C Robert / Neutzner, Albert / Remonda, Luca / Killer, Hanspeter E

Brain communications

2022 Volume 4, Issue 5, Page(s) fcac240

Abstract: The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, ...

Abstract	The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, there is no clear relationship between the severity of papilloedema and CSF pressure. Furthermore, there are cases of purely unilateral papilloedema and cases without papilloedema despite significantly elevated intracranial pressure as well as papilloedema that can persist despite a successfully lowered intracranial pressure. We hypothesize that at least in some of such cases, in addition to purely pressure-induced damage to the optic nerve, the biochemical composition of the CSF in the subarachnoid space surrounding the orbital optic nerve may play a role in the pathogenesis of vision loss. In this retrospective study, we report on lipocalin-type prostaglandin D synthase concentrations in the CSF within the perioptic and lumbar subarachnoid space in 14 patients with idiopathic intracranial hypertension (13 females, mean age 45 ± 13 years) with chronic persistent papilloedema resistant to maximum-tolerated medical therapy and visual impairment. CSF was collected from the subarachnoid space of the optic nerve during optic nerve sheath fenestration and from the lumbar subarachnoid space at the time of lumbar puncture. CSF was analysed for lipocalin-type prostaglandin D synthase and the concentrations compared between the two sites using nephelometry. The mean lipocalin-type prostaglandin D synthase concentration in the perioptic subarachnoid space was significantly higher compared with the concentration in the lumbar subarachnoid space (69 ± 51 mg/l without correction of serum contamination and 89 ± 67 mg/l after correction of serum contamination versus 23 ± 8 mg/l;
Language	English
Publishing date	2022-09-26
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcac240
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