Various studies suggested that brain-derived neurotrophic factor (BDNF) gene polymorphisms contributed to the development of many neurological disorders.
Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF-L] and total tau protein [t-tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system.
Mutations in the GFAP gene lead to Alexander disease (AxD), a rare, fatal neurological disorder characterized by the presence of abnormal astrocytes that contain GFAP protein aggregates, termed Rosenthal fibers (RFs), and the loss of myelin.
An optimised liposomal formulation [DPPC/P-lyso-PC/DSPE-PEG2000 90/10/4 (mol/mol) (LTSL)] was chosen for further application in encapsulating therapeutic proteins, such as lysozyme and the brain-derived neurotrophic factor (BDNF), which are recognized as drug carriers and potential therapeutic agents for kidney diseases and neurological disorders.
Mutation in superoxide dismutase-1 (SOD1) causes the inherited degenerative neurological disease familial amyotrophic lateral sclerosis (ALS), a non-cell-autonomous disease: mutant SOD1 synthesis in motor neurons and microglia drives disease onset and progression, respectively.
We also measured the concentrations and activities of Cu/ZnSOD in FALS patients with no identifiable SOD1 mutations, sporadic ALS (SALS) patients, and patients with other neurologic disorders.
Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina.
This work identifies SCN8A as the fifth sodium-channel gene to be mutated in epilepsy and demonstrates the value of WGS for the identification of pathogenic mutations causing severe, sporadic neurological disorders.
This article gives an outline of molecular biological approaches to analysis of neurological disorders such as giant cell glioblastoma (GGBM) and amyotrophic lateral sclerosis (ALS), and their respective animal models: p53 knockout mice for GGBM and mutant superoxide dismutase-1 transgenic mice for ALS.
Mutations of Scn8a in the mouse demonstrate the broad spectrum of neurological disease that can result from different alleles of the same sodium channel gene.
Transcriptional dysregulation of these genes was also observed in cells derived from patients presenting with other neurological disorders linked to mutations in other Mediator subunits or proteins interacting with MED.
Moreover, when administered for 3 days, PAS with 100 Hz led to significant MEP potentiation on the 3<sup>rd</sup> day (P = 0.043) even when the TMS target was selected suboptimally (modelling cases where finding an optimal site for TMS is problematic due to a neurological disease).
Given recent reports of Kv2.1 dysregulation in neurological disorders, it is possible that alterations in the functional interaction between DAT and Kv2.1 affect dopamine neuron activity.
GLUT1 deficiency syndrome is a treatable disorder of glucose transport into the brain caused by a variety of mutations in the SLC2A1 gene which are the cause of different neurological disorders also with different types of epilepsy and related clinical phenotypes.
The coding region of the DAT gene, SLC6A3, is well conserved, but non-coding regions are more variable, most notably a variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region, which has been studied in a number of dopamine-related neurological disorders, including Parkinson's disease (PD).
In conclusion, the homozygous DHFR mutation p.Asp153Val causes DHFR deficiency and leads to a complex hematological and neurological disease that can be successfully treated with folinic acid.
The 5 new diagnoses implicated 2 genes associated with canonical mitochondrial disorders (NDUFV1, POLG2), and 3 genes known to underlie other neurologic disorders (DPYD, KARS, WFS1), underscoring the phenotypic and biochemical overlap with other inborn errors.
We report the lack of megaloblastic anaemia in a patient with severe methionine synthase deficiency who is also homozygous for C677T in MTHFR, hypothesize that the MTHFR polymorphism protects the patient against anaemia and speculate that homozygosity for MTHFRC677T could cause the dissociation between haematological and neurological disease seen in some patients with vitamin B12 deficiency.
Heritable mutations in the ttpA gene, encoding for TTP, result in ataxia with vitamin E deficiency (AVED) syndrome, typified by low vitamin E levels and a plethora of neurological disorders.
Three human disorders including a neoplasia (a T-cell acute lymphoblastic leukemia/lymphoma), a late onset neurological disease (CADASIL) and a developmental disorder (the Alagille syndrome) are associated with mutations in, respectively, the Notch1, Notch3 and Jagged1 genes, pointing out the broad spectrum of Notch activity in humans.
The E6AP ubiquitin-protein ligase (E3) mediates the human papillomavirus-induced degradation of the p53 tumor suppressor in cervical cancer and is mutated in Angelman syndrome, a neurological disorder.