Most cited article - PubMed ID 37054941
GPR160 is not a receptor of anorexigenic cocaine- and amphetamine-regulated transcript peptide
The preparation of specifically iodine-125 (125I)-labeled peptides of high purity and specific activity represents a key tool for the detailed characterization of their binding properties in interaction with their binding partners. Early synthetic methods for the incorporation of iodine faced challenges such as harsh reaction conditions, the use of strong oxidants and low reproducibility. Herein, we review well-established radiolabeling strategies available to incorporate radionuclide into a protein of interest, and our long-term experience with a mild, simple and generally applicable technique of 125I late-stage-labeling of biomolecules using the Pierce iodination reagent for the direct solid-phase oxidation of radioactive iodide. General recommendations, tips, and details of optimized chromatographic conditions to isolate pure, specifically 125I-mono-labeled biomolecules are illustrated on a diverse series of (poly)peptides, ranging up to 7.6 kDa and 67 amino acids (aa). These series include peptides that contain at least one tyrosine or histidine residue, along with those featuring disulfide crosslinking or lipophilic derivatization. This mild and straightforward late-stage-labeling technique is easily applicable to longer and more sensitive proteins, as demonstrated in the cases of the insulin-like growth factor binding protein-3 (IGF-BP-3) (29 kDa and 264 aa) and the acid-labile subunit (ALS) (93 kDa and 578 aa).
Since 1975, the incidence of obesity has increased to epidemic proportions, and the number of patients with obesity has quadrupled. Obesity is a major risk factor for developing other serious diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Recent epidemiologic studies have defined obesity as a risk factor for the development of neurodegenerative diseases, such as Alzheimer's disease (AD) and other types of dementia. Despite all these serious comorbidities associated with obesity, there is still a lack of effective antiobesity treatment. Promising candidates for the treatment of obesity are anorexigenic neuropeptides, which are peptides produced by neurons in brain areas implicated in food intake regulation, such as the hypothalamus or the brainstem. These peptides efficiently reduce food intake and body weight. Moreover, because of the proven interconnection between obesity and the risk of developing AD, the potential neuroprotective effects of these two agents in animal models of neurodegeneration have been examined. The objective of this review was to explore anorexigenic neuropeptides produced and acting within the brain, emphasizing their potential not only for the treatment of obesity but also for the treatment of neurodegenerative disorders.
- Keywords
- Alzheimer´s-like pathology, anorexigenic neuropeptides, antiobesity treatment, neuroprotection,
- MeSH
- Alzheimer Disease drug therapy metabolism pathology prevention & control MeSH
- Hypothalamus drug effects metabolism pathology MeSH
- Anti-Obesity Agents * pharmacology therapeutic use MeSH
- Humans MeSH
- Brain drug effects metabolism pathology MeSH
- Neurodegenerative Diseases drug therapy metabolism prevention & control MeSH
- Neuropeptides * metabolism pharmacology therapeutic use MeSH
- Neuroprotective Agents * pharmacology therapeutic use MeSH
- Obesity * drug therapy metabolism MeSH
- Eating drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Anti-Obesity Agents * MeSH
- Neuropeptides * MeSH
- Neuroprotective Agents * MeSH