A Pathogenic Mechanism Potentially Operative in Multiple Progressive Diseases and Its Therapeutic Implications

A variety of peptide signaling moieties that we have termed intracrines can act in the interiors of their cells of synthesis or of target cells after internalization. These intracrine factors are known to be upregulated in such disorders as diabetic nephropathy, systolic heart failure, and age‐relat...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2017-12, Vol.57 (12), p.1507-1518
Main Author: Re, Richard N.
Format: Article
Language:English
Subjects:
Age‐related macular degeneration
Cardiovascular Diseases - metabolism
Cardiovascular Diseases - pathology
Chronic renal disease
Commonality
Diabetic nephropathy
Disease
Heart failure
Humans
Intracrine
Kidney Diseases - metabolism
Kidney Diseases - pathology
Macular Degeneration - metabolism
Macular Degeneration - pathology
Neurodegenerative diseases
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - pathology
Parkinson's disease
Protein Sorting Signals
Renin‐angiotensin system
Up-Regulation
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Description
Summary:A variety of peptide signaling moieties that we have termed intracrines can act in the interiors of their cells of synthesis or of target cells after internalization. These intracrine factors are known to be upregulated in such disorders as diabetic nephropathy, systolic heart failure, and age‐related macular degeneration. Indeed, a similar set of intracrines is upregulated in each of these disorders, suggesting a commonality of mechanism. In addition, several chronic neurodegenerative disorders such as Alzheimer disease and Parkinson disease involve intercellular trafficking of intracellular disease‐causing proteins. These disorders can be considered intracrine‐like. Here the mechanistic and therapeutic implications of these observations, and of the relevant modes of intracrine action, are discussed, including the possibility that similar therapeutic approaches could be effective in multiple progressive disorders and the implications of these observations for intracrine pharmacology in general.
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.997