A central nervous system (CNS) disease can affect either the brain or the spinal cord, resulting in neurological or psychiatric disorders. Causes of CNS diseases are trauma, infections, degeneration, autoimmune disorders, structural defects, tumors, and stroke. Here we focus on neurodegenerative diseases, mood disorders, schizophrenia, and autism.
See details here.
Neurodegenerative diseases are featured by progressive dysfunction and death
of cells in selected areas in the nervous system. These include Alzheimer's
disease (AD), Parkinson's disease (PD), Huntington's disease, and Amyotrophic
lateral sclerosis (ALS). Alzheimer's disease causes memory loss, personality
changes, dementia and, ultimately, death. Parkinson's disease causes tremor,
stiffness, and impaired control of movement resulting from loss of dopamine.
Huntington's is a hereditary disease caused by a dominant mutation on either of
the two copies of Huntingtin gene. The mutation results in neuronal degeneration
in the frontal lobe of the brain. The most characteristic symptom of
Huntington's disease is jerky, random, and uncontrollable movements called
chorea. Amyotrophic lateral sclerosis is a motor neurons degenerative disease
with no known cause. SABiosciences' Alzheimer's disease PCR arrays can be used
to detect AD-related gene expressions.
Extra- and intra-cellular accumulation of misfolded proteins, such as beta-amyloid,
tau, alpha-synuclein, TDP-43, are the hallmarks of many neurodegenerative disorders.
The abnormal protein dynamics associated with defective degradation are due to
deficiency of the ubiquitin-proteosomal-autophagy system. Alzheimer's disease is
regarded as a protein disease, caused by accumulation of abnormally folded beta-amyloid
protein and tau proteins in the brain. Mitochondrial dysfunction is another
prominent feature of various neurodegenerative diseases because the most common
form of cell death in neurodegeneration is through the intrinsic mitochondrial
apoptotic pathway. In general, disruption of neuronal Golgi apparatus and
transport, deregulation of molecular chaperones, defective protein degradation,
oxidative stress and free radical formation, impaired bioenergetics and
mitochondrial dysfunction, deregulation of neurotransmitters, neurotrophins, and
neuroinflammatory processes (such as Multiple Sclerosis, please see the review
under Cytokines & Inflammation) can all lead to programmed cell death. It is
worth noting that methylation of CpG islands is one of the important mechanisms
that promote the accumulation of oxidized DNA. For example, environmental
influences during brain development can inhibit DNA methyltransferases, thus
hypomethylating promoters of genes associated with Alzheimer's disease, causing
the accumulation of beta-amyloid precursor protein. SABiosciences provides a broad
range of PCR arrays to study Apoptosis, Mitochondria, Mitochondrial Energy
Metabolism, Ubiquitination Pathway, Unfolded Protein Response, Antioxidative
Stress and Antioxidant Defense, Neurotransmitter Receptors and Regulators,
Neurotrophins and Receptors, and Neuroscience Ion Channels and Transporters.
CNS diseases, especially psychiatric diseases, are prefect subjects for three
hot topics of genetic research: (1) gene-environment interaction, which
considers how genetic factors shape exposure and responses toward the social
environment; (2) endophenotypic research, which identifies neurophysiological
and psychological mediators of genetic risk; and (3) epigenetic research, which
explain how early environment can foster changes in gene expression, altering
subsequent emotional development. SABiosciences provides both methylation PCR
arrays and chromatin immunoprecipiotation (ChIP) PCR arrays to address
epigenetic studies.
Mood disorders such as depression, bipolar disorder, anxiety disorder and
panic disorder are more and more prevalent in modern society. While monoamine
(serotonin and dopamine neurotransmitters) signaling has dominated the
scientific investigation of depression and monoamine-based antidepressants
remain the first line of therapy, new gene candidates such as PCLO and GRM7 are
beginning to change the future direction of depression research. It has been
known that chronic treatment with antidepressants increases BDNF-mediated
signaling and upregulates the transcription factor CREB (cyclic-AMP-response
element-binding protein), which is downstream of several serotonin and other
stimulatory G-protein-coupled receptors (GPCRs). SABiosciences' GPCR array can
help you study G-protein-coupled receptors.
Cytokines are also important modulators of mood. Roughly 30% of individuals
treated with recombinant interferons develop depression as a side effect of
treatment. Immune system activation is a signature of a small subset of
depression cases, including those associated with autoimmune conditions such as
rheumatoid arthritis, in which heightened system-wide inflammation can increase
the risk of acute coronary events in addition to producing depressive mood
changes. Recent preclinical studies indicate that blocking pro-inflammatory
cytokine-mediated signaling (such as interferon-alpha, TNF-alpha, IL-6, and IL-1beta, which
activate the hypothalamic-pituitary-adrenal axis and central monoamine systems)
can produce antidepressant effects. SABiosciences' Inflammatory Cytokines and
Receptors PCR arrays and Inflammatory Response and Autoimmunity PCR arrays can
be used to facilitate your research.
Epigenetic research indicates that transcription of the genes involved in
neuroplastic responses to stress or antidepressant treatments can be regulated
through chromatin remodeling. For example, the methylation of histones on
specific lysine residues is important in the repression of Bdnf expression in
the hippocampus after social defeat; inhibitors of histone deacetylases (HDAC)
have shown antidepressant effects in several assessments.
Schizophrenia is a psychotic disorder marked by some or all of the following
symptoms: delusions, hallucinations, disorganized, severe emotional
abnormalities, incoherent speech, and withdrawal into an inner world. Autism is
distinguished by a characteristic triad of symptoms: impairments in social
interaction; impairments in communication; and restricted interests and
repetitive behavior. Both schizophrenia and autism are conditions of complex
inheritance. Recent convergent lines of evidence appear that schizophrenia and
autism are caused by under-development, but not dysregulated over-development of
the human social brain. SNP (Single Nucleotide Polymorphism), CNV (Copy Number
Variant), and epigenetic profiling have been intensively used to study these
diseases. Please send samples to us for gene expression, SNP, CNV, or CGH
service with Illumina chips, or for methylation profiling service with
SABioscience's Methyl- Profiler methylation PCR arrays.
Cognitive deficits and mood dysregulation are hallmarks of psychiatric
disorders. As the hippocampus is a site of structural and functional pathology
in most mental illnesses, a hippocampal-based treatment has been proposed. In
particular, preclinical and clinical research suggests that hippocampal
neurogenesis, the generation of new neurons in the adult dentate gyrus to
reverse hippocampal atrophy and functional deficits, is promising in treating
mental illnesses including Alzheimer's disease. SABiosciences' Neurogenesis and
Neural Stem Cell PCR arrays can be applied to neural stem cell research.
