Bile acids (BA) are amphipathic steroid acids synthesized from cholesterol in the liver. They act as detergents to expedite the digestion and absorption of dietary lipids and lipophilic vitamins. BA are also considered to be signaling molecules, being ligands of nuclear and cell-surface receptors, including farnesoid X receptor and Takeda G-protein receptor 5. Moreover, BA also activate ion channels, including the bile acid-sensitive ion channel and epithelial Na+ channel. BA regulate glucose and lipid metabolism by activating these receptors in peripheral tissues, such as the liver and brown and white adipose tissue. Recently, 20 different BA have been identified in the central nervous system. Furthermore, BA affect the function of neurotransmitter receptors, such as the muscarinic acetylcholine receptor and γ-aminobutyric acid receptor. BA are also known to be protective against neurodegeneration. Here, we review recent findings regarding the biosynthesis, signaling, and neurological functions of BA.
Macroautophagy, hereafter referred to as autophagy, is a bulk degradation process performed by lysosomes in which aggregated and altered proteins as well as dysfunctional organelles are decomposed. Autophagy is a basic cellular process that maintains homeostasis and is crucial for postmitotic neurons. Thus, impaired autophagic processes in neurons lead to improper homeostasis and neurodegeneration. Recent studies have suggested that impairments of the autophagic process are associated with several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and static encephalopathy of childhood with neurodegeneration in adulthood. In this review, we focus on the recent findings regarding the autophagic process and the involvement of autophagy in neurodegenerative diseases.
Amylin, (or islet amyloid polypeptide; IAPP), a 37-amino acid peptide hormone, is released in response to nutrients, including glucose, lipids or amino acids. Amylin is co-stored and co-secreted with insulin by pancreatic islet β-cells. Amylin inhibits food intake, delays gastric emptying, and decreases blood glucose levels, leading to the reduction of body weight. Therefore, amylin as well as insulin play important roles in controlling the level of blood glucose. However, human amylin aggregates and human amylin oligomers cause membrane disruption, endoplasmic reticulum (ER) stress and mitochondrial damage. Since cytotoxicity of human amylin oligomers to pancreatic islet β-cells can lead to diabetes, the protection of pancreatic islet β cells from cytotoxic amylin is crucial. Human amylin oligomers also inhibit autophagy, although autophagy can function to remove amylin aggregates and damaged organelles. Small molecules, including β-sheet breaker peptides, chemical chaperones, and foldamers, inhibit and disaggregate amyloid formed by human amylin, suggesting the possible use of these small molecules in the treatment of diabetes. In this review, we summarize recent findings regarding the role and cytotoxicity of amylin and the protection of pancreatic islet β-cells from cytotoxicity of amylin.
Amino acids are important components for peptides and proteins and act as signal transmitters. Only L-amino acids have been considered necessary in mammals, including humans. However, diverse D-amino acids, such as D-serine, D-aspartate, D-alanine, and D-cysteine, are found in mammals. Physiological roles of these D-amino acids not only in the nervous system but also in the endocrine system are being gradually revealed. N-Methyl-D-aspartate (NMDA) receptors are associated with learning and memory. D-Serine, D-aspartate, and D-alanine can all bind to NMDA receptors. H2S generated from D-cysteine reduces disulfide bonds in receptors and potentiates their activity. Aberrant receptor activity is related to diseases of the central nervous system (CNS), such as Alzheimer's disease, amyotrophic lateral sclerosis, and schizophrenia. Furthermore, D-amino acids are detected in parts of the endocrine system, such as the pineal gland, hypothalamus, pituitary gland, pancreas, adrenal gland, and testis. D-Aspartate is being investigated for the regulation of hormone release from various endocrine organs. Here we focused on recent findings regarding the synthesis and physiological functions of D-amino acids in the nervous and endocrine systems.
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