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Article ; Online: Derailed Ceramide Metabolism in Atopic Dermatitis (AD): A Causal Starting Point for a Personalized (Basic) Therapy.

Blaess, Markus / Deigner, Hans-Peter

International journal of molecular sciences

2019 Volume 20, Issue 16

Abstract: Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the ... ...

Abstract	Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration.
MeSH term(s)	Amitriptyline/therapeutic use ; Animals ; Antioxidants/metabolism ; Apoptosis/physiology ; Ceramides/metabolism ; Dermatitis, Atopic/metabolism ; Humans ; Linoleic Acid/therapeutic use ; Sphingolipids/metabolism
Chemical Substances	Antioxidants ; Ceramides ; Sphingolipids ; Amitriptyline (1806D8D52K) ; Linoleic Acid (9KJL21T0QJ)
Language	English
Publishing date	2019-08-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20163967
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Derailed Ceramide Metabolism in Atopic Dermatitis (AD)

Markus Blaess / Hans-Peter Deigner

International Journal of Molecular Sciences, Vol 20, Iss 16, p

A Causal Starting Point for a Personalized (Basic) Therapy

2019 Volume 3967

Abstract	Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration.
Keywords	atopic dermatitis ; lysosomotropic compounds ; apoptosis ; lysosome ; ceramide metabolism ; amitriptyline ; ceramide de novo synthesis ; antioxidants ; linoleic acid ; sphingolipid profile ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Derailed Ceramide Metabolism in Atopic Dermatitis (AD). A Causal Starting Point for a Personalized (Basic) Therapy

Blaess, Markus / Deigner, Hans-Peter

2019

Abstract: Art. 3967, 15 S. ... Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids ... ...

Abstract	Art. 3967, 15 S. Active rebuilding, stabilizing, and maintaining the lipid barrier of the skin is an encouraging disease management and care concept for dry skin, atopic dermatitis (eczema, neurodermatitis), and psoriasis. For decades, corticosteroids have been the mainstay of topical therapy for atopic dermatitis; however, innovations within the scope of basic therapy are rare. In (extremely) dry, irritated, or inflammatory skin, as well as in lesions, an altered (sphingo)lipid profile is present. Recovery of a balanced (sphingo)lipid profile is a promising target for topical and personalized treatment and prophylaxis. New approaches for adults and small children are still lacking. With an ingenious combination of commonly used active ingredients, it is possible to restore and reinforce the dermal lipid barrier and maintain refractivity. Lysosomes and ceramide de novo synthesis play a key role in attenuation of the dermal lipid barrier. Linoleic acid in combination with amitriptyline in topical medication offers the possibility to relieve patients affected by dry and itchy skin, mild to moderate atopic dermatitis lesions, and eczemas without the commonly occurring serious adverse effects of topical corticosteroids or systemic antibody administration. 20 Nr.16
Keywords	Atopic dermatitis ; Lysosomotropic compounds ; Apoptose ; ceramide metabolism ; Amitriptyline ; Ceramide de novo synthesis ; antioxidants ; linoleic acid ; Sphingolipid profile ; 610 ; 547 ; 620
Subject code	610
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Drug triggered pruritus, rash, papules, and blisters - is AGEP a clash of an altered sphingolipid-metabolism and lysosomotropism of drugs accumulating in the skin?

Blaess, Markus / Kaiser, Lars / Sommerfeld, Oliver / Csuk, René / Deigner, Hans-Peter

Lipids in health and disease

2021 Volume 20, Issue 1, Page(s) 156

Abstract: Rash, photosensitivity, erythema multiforme, and the acute generalized exanthematous pustulosis (AGEP) are relatively uncommon adverse reactions of drugs. To date, the etiology is not well understood and individual susceptibility still remains unknown. ... ...

Abstract	Rash, photosensitivity, erythema multiforme, and the acute generalized exanthematous pustulosis (AGEP) are relatively uncommon adverse reactions of drugs. To date, the etiology is not well understood and individual susceptibility still remains unknown. Amiodarone, chlorpromazine, amitriptyline, and trimipramine are classified lysosomotropic as well as photosensitizing, however, they fail to trigger rash and pruritic papules in all individuals. Lysosomotropism is a common charcteristic of various drugs, but independent of individuals. There is evidence that the individual ability to respond to external oxidative stress is crosslinked with the elongation of long-chain fatty acids to very long-chain fatty acids by ELOVLs. ELOVL6 and ELOVL7 are sensitive to ROS induced depletion of cellular NADPH and insufficient regeneration via the pentose phosphate pathway and mitochondrial fatty acid oxidation. Deficiency of NADPH in presence of lysosomotropic drugs promotes the synthesis of C
MeSH term(s)	Acute Generalized Exanthematous Pustulosis/drug therapy ; Acute Generalized Exanthematous Pustulosis/etiology ; Acute Generalized Exanthematous Pustulosis/pathology ; Amitriptyline/pharmacokinetics ; Blister/chemically induced ; Ceramides/metabolism ; Dermatitis, Atopic/etiology ; Fatty Acids/chemistry ; Fatty Acids/metabolism ; Histamine Antagonists/adverse effects ; Humans ; Lysosomes/drug effects ; Lysosomes/metabolism ; NADP/metabolism ; Photosensitivity Disorders/etiology ; Photosensitivity Disorders/metabolism ; Photosensitizing Agents/adverse effects ; Sphingolipids/metabolism
Chemical Substances	Ceramides ; Fatty Acids ; Histamine Antagonists ; Photosensitizing Agents ; Sphingolipids ; Amitriptyline (1806D8D52K) ; NADP (53-59-8)
Language	English
Publishing date	2021-11-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2091381-3
ISSN	1476-511X ; 1476-511X
ISSN (online)	1476-511X
ISSN	1476-511X
DOI	10.1186/s12944-021-01552-3
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Article ; Online: Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules: Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19.

Blaess, Markus / Kaiser, Lars / Sommerfeld, Oliver / Csuk, René / Deigner, Hans-Peter

International journal of molecular sciences

2021 Volume 22, Issue 4

Abstract: Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal ... ...

Abstract	Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.
MeSH term(s)	Antiviral Agents/pharmacokinetics ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/drug therapy ; COVID-19/immunology ; COVID-19/metabolism ; COVID-19/virology ; Chlorpromazine/pharmacokinetics ; Chlorpromazine/pharmacology ; Chlorpromazine/therapeutic use ; Cytokine Release Syndrome/drug therapy ; Drug Discovery/methods ; Drug Repositioning/methods ; Fluvoxamine/pharmacokinetics ; Fluvoxamine/pharmacology ; Fluvoxamine/therapeutic use ; Humans ; Hydroxychloroquine/pharmacokinetics ; Hydroxychloroquine/pharmacology ; Hydroxychloroquine/therapeutic use ; Interleukin-1/antagonists & inhibitors ; Interleukin-1/immunology ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/immunology ; Lung/drug effects ; Lung/immunology ; Lung/metabolism ; Lung/virology ; Lysosomes/drug effects ; Lysosomes/immunology ; Lysosomes/metabolism ; Lysosomes/virology ; SARS-CoV-2/drug effects ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Small Molecule Libraries/pharmacokinetics ; Small Molecule Libraries/pharmacology ; Small Molecule Libraries/therapeutic use ; Virus Replication/drug effects
Chemical Substances	Antiviral Agents ; Interleukin-1 ; Interleukin-6 ; Small Molecule Libraries ; Hydroxychloroquine (4QWG6N8QKH) ; Fluvoxamine (O4L1XPO44W) ; Chlorpromazine (U42B7VYA4P)
Language	English
Publishing date	2021-02-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22041797
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Rational Drug Repurposing: Focus on Lysosomotropism, Targets in Disease Process, Drug Profile, and Pulmonary Tissue Accumulation in SARS-CoV-2 Infection/COVID-19.

Blaess, Markus / Kaiser, Lars / Sommerfeld, Oliver / Rentschler, Simone / Csuk, René / Deigner, Hans-Peter

Frontiers in pharmacology

2020 Volume 11, Page(s) 584881

Language	English
Publishing date	2020-11-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2020.584881
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Article ; Online: Lysosomotropic Active Compounds — Hidden Protection against COVID-19 / SARS-CoV-2 Infection?

Bläss, Markus / Kaiser, Lars / Sauer, Martin / Deigner, Hans-Peter

2020

Keywords	covid19
Language	German
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks.

Blaess, Markus / Kaiser, Lars / Sauer, Martin / Csuk, René / Deigner, Hans-Peter

International journal of molecular sciences

2020 Volume 21, Issue 14

Abstract: In line with SARS and MERS, the SARS-CoV-2/COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide. SARS-CoV-2 infection/COVID-19 provides numerous therapeutic targets, each of them promising, but not leading to the ... ...

Abstract	In line with SARS and MERS, the SARS-CoV-2/COVID-19 pandemic is one of the largest challenges in medicine and health care worldwide. SARS-CoV-2 infection/COVID-19 provides numerous therapeutic targets, each of them promising, but not leading to the success of therapy to date. Neither an antiviral nor an immunomodulatory therapy in patients with SARS-CoV-2 infection/COVID-19 or pre-exposure prophylaxis against SARS-CoV-2 has proved to be effective. In this review, we try to close the gap and point out the likely relationships among lysosomotropism, increasing lysosomal pH, SARS-CoV-2 infection, and disease process, and we deduce an approach for the treatment and prophylaxis of COVID-19, and cytokine release syndrome (CRS)/cytokine storm triggered by bacteria or viruses. Lysosomotropic compounds affect prominent inflammatory messengers (e.g., IL-1B, CCL4, CCL20, and IL-6), cathepsin-L-dependent viral entry of host cells, and products of lysosomal enzymes that promote endothelial stress response in systemic inflammation. As supported by recent clinical data, patients who have already taken lysosomotropic drugs for other pre-existing conditions likely benefit from this treatment in the COVID-19 pandemic. The early administration of a combination of antivirals such as remdesivir and lysosomotropic drugs, such as the antibiotics teicoplanin or dalbavancin, seems to be able to prevent SARS-CoV-2 infection and transition to COVID-19.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Betacoronavirus/isolation & purification ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus 3C Proteases ; Coronavirus Infections/complications ; Coronavirus Infections/drug therapy ; Coronavirus Infections/pathology ; Coronavirus Infections/virology ; Cytokine Release Syndrome/etiology ; Cytokine Release Syndrome/pathology ; Humans ; Lysosomes/metabolism ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/complications ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/pathology ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Viral Nonstructural Proteins/antagonists & inhibitors ; Viral Nonstructural Proteins/metabolism ; Virus Internalization/drug effects
Chemical Substances	Antiviral Agents ; Viral Nonstructural Proteins ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Keywords	covid19
Language	English
Publishing date	2020-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21144953
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Article ; Online: Drugs, Metabolites, and Lung Accumulating Small Lysosomotropic Molecules

Markus Blaess / Lars Kaiser / Oliver Sommerfeld / René Csuk / Hans-Peter Deigner

International Journal of Molecular Sciences, Vol 22, Iss 4, p

Multiple Targeting Impedes SARS-CoV-2 Infection and Progress to COVID-19

2021 Volume 1797

Abstract	Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic.
Keywords	SARS-CoV-2 ; COVID-19 ; lysosomotropism ; metabolites ; cytokine storm ; viral host cell entry ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 572
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Drugs, metabolites, and lung accumulating small lysosomotropic molecules

Blaess, Markus / Kaiser, Lars / Sommerfeld, Oliver / Csuk, René / Deigner, Hans-Peter

Multiple targeting impedes SARS-CoV-2 infection and progress to COVID-19

2021

Abstract: Art. 1797, 12 S. ... Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers ... ...

Abstract	Art. 1797, 12 S. Lysosomotropism is a biological characteristic of small molecules, independently present of their intrinsic pharmacological effects. Lysosomotropic compounds, in general, affect various targets, such as lipid second messengers originating from lysosomal enzymes promoting endothelial stress response in systemic inflammation; inflammatory messengers, such as IL-6; and cathepsin L-dependent viral entry into host cells. This heterogeneous group of drugs and active metabolites comprise various promising candidates with more favorable drug profiles than initially considered (hydroxy) chloroquine in prophylaxis and treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections/Coronavirus disease 2019 (COVID-19) and cytokine release syndrome (CRS) triggered by bacterial or viral infections. In this hypothesis, we discuss the possible relationships among lysosomotropism, enrichment in lysosomes of pulmonary tissue, SARS-CoV-2 infection, and transition to COVID-19. Moreover, we deduce further suitable approved drugs and active metabolites based with a more favorable drug profile on rational eligibility criteria, including readily available over-the-counter (OTC) drugs. Benefits to patients already receiving lysosomotropic drugs for other pre-existing conditions underline their vital clinical relevance in the current SARS-CoV2/COVID-19 pandemic. 22 Nr.4
Keywords	SARS-CoV-2 ; COVID-19 ; Lysomotropism ; metabolites ; Cytokine storm ; viral host cell entry ; approved drugs ; pulmonary tissue accumulation ; drug repurposing ; eligibility criteria ; 610 ; 547 ; 620
Subject code	610 ; 572
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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