Dr. Ta-Yuan Chang E-Mail
Professor, Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
Research Keywords: cholesterol metabolism; membrane proteins; Alzheimer's disease; NPC disease; Vascular dementia
Dr. Catherine Chang E-Mail
Principal Research Scientist, Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA
Research Keywords: cholesterol metabolism; structure and function analysis of ACAT/SOAT; membrane proteins; Alzheimer's disease; NPC disease
Cholesterol is a lipid molecule that is essential to the structure and function of biological membranes, as well as the growth and maintenance of all mammalian cells. The metabolites of cholesterol, including oxysterols, neurosteroids, and bile acids, play important regulatory roles in mammalian physiology. Increasing evidence implicates the involvement of cholesterol dyshomeostasis in diverse neurological diseases, including Alzheimer disease, autism, Huntington disease, multiple sclerosis, Niemann-Pick type C disease, Smith-Lemli-Opitz syndrome, and vascular dementia. The mechanistic connections between cholesterol and the pathophysiology of these diseases, are as yet inadequately understood.
To stimulate research in this burgeoning area, we are organizing a special issue of the Journal, entitled “Cholesterol Dyshomeostasis in Neurological Diseases,” that will contain 6 to 10 invited reviews written by leading scientists in the relevant research fields. We are also soliciting additional relevant manuscripts that describe original research, meta-analysis, commentary, or editorial. Manuscripts that address the following areas will be particularly welcome: roles of cholesterol or its metabolites in the brain; brain-penetrating agents to facilitate CNS cholesterol homeostasis; and neurological alterations caused by cholesterol imbalance in the CNS or by hypercholesterolemia and atherosclerosis.
The deadline for manuscript submission is September 30th, 2021. Each qualified manuscript will undergo prompt and thorough peer-review. The published issue will receive wide promotion by the Journal to the international scientific community. The goal of this special issue is ultimately to stimulate the discovery and development of novel, cholesterol-related neuroprotective therapies by scientists working in the basic, translational, and clinical neuroscience arenas. This issue can also be used as a timely resource for graduate students and postdoctoral fellows entering the field of neurodegeneration research.
Keywords: cholesterol; membranes; neuroscience; neuroprotective therapies; neurological disease
Phosphoinositides are membrane phospholipids involved in a variety of cellular processes like growth, development, metabolism, and transport. This review focuses on the maintenance of cellular homeostasis of phosphatidylinositol 4,5-bisphosphate (PIP2), and phosphatidylinositol 3,4,5-trisphosphate (PIP3). The critical balance of these PIPs is crucial for regulation of neuronal form and function. The activity of PIP2 and PIP3 can be regulated through kinases, phosphatases, phospholipases and cholesterol microdomains. PIP2 and PIP3 carry out their functions either indirectly through their effectors activating integral signaling pathways, or through direct regulation of membrane channels, transporters, and cytoskeletal proteins. Any perturbations to the balance between PIP2 and PIP3 signaling result in neurodevelopmental and neurodegenerative disorders. This review will discuss the upstream modulators and downstream effectors of the PIP2 and PIP3 signaling, in the context of neuronal health and disease.
The autism spectrum disorder (ASD) comprises a series of neurological diseases that share serious alterations of the development of the central nervous system. The degree of disability may vary so that Asperger’s may have a relatively normal life and get positions of responsibility in corporations and even in Governments, whereas other ASD sufferers are fully dependent on caregivers and have serious cognitive deficits. Although the first cases of autism were detected by looking at failures in metabolism, e.g., phenylketonuria, to later identify the faulty gene, today the trend is the opposite, first obtaining the exome and minimizing the look for altered parameters in blood, urine, etc. Cholesterol is key for neural development as it is not able to cross the blood brain barrier. Therefore, any gene or environmental factor that affects cholesterol synthesis will impact early developmental stages eventually leading to a disease within the autism spectrum and/or schizophrenia. This review provides data of the relevance of cholesterol dyshomeostasis in autism spectrum disorders. Determining biochemical parameters in body fluids should help to provide new therapeutic approaches in some cases of autism.