Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0040822 (
tremor
)
18,428
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Spinal and bulbar (bulbospinal) muscular atrophy (BSMA,
SBMA
, Kennedy's disease) is a progressive motor neuron disease with rare involvement of structures other than the lower motor neuron, such as the endocrine system and the central nervous system (CNS). Aim of the review was to study type and frequency of clinical, imaging, and functional (CNS) abnormalities in
SBMA
patients. The most frequent clinical CNS manifestations in
SBMA
are postural or kinetic
tremor
predominantly of the hands and mild cognitive impairment. The most frequent instrumental CNS abnormality in
SBMA
patients are white matter lesions, visible on voxel-based morphometry, magnetic resonance spectroscopy, or diffusion tensor imaging. Single patients with enlarged pituitary volume, or diminished somato-sensory representation in the cortex have been also reported. Seizures, epilepsy, ataxia, spasticity, dystonia, or migraine have not been found in
SBMA
patients. Only supportive treatment is available for CNS manifestations in
SBMA
. It is concluded that the most frequent CNS abnormalities in
SBMA
are
tremor
, cognitive impairment, and white matter lesions on new imaging modalities. CNS involvement in
SBMA
should not be neglected as a phenotypic manifestation of
SBMA
and, apart from cognitive involvement, may help to differentiate clinically
SBMA
from other types of motor neuron disease.
...
PMID:Central nervous system abnormalities in spinal and bulbar muscular atrophy (Kennedy's disease). 3135 Dec 15
Dozens of incurable neurological disorders result from expansion of short repeat sequences in both coding and non-coding regions of the transcriptome. Short repeat expansions underlie microsatellite repeat expansion (MRE) disorders including myotonic dystrophy (DM1, CUG
50-3,500
in
DMPK
; DM2, CCTG
75-11,000
in ZNF9), fragile X
tremor
ataxia syndrome (FXTAS, CGG
50-200
in FMR1), spinal bulbar muscular atrophy (
SBMA
, CAG
40-55
in AR), Huntington's disease (HD, CAG
36-121
in HTT), C9ORF72- amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD and C9-ALS/FTD, GGGGCC in C9ORF72), and many others, like ataxias. Recent research has highlighted several mechanisms that may contribute to pathology in this heterogeneous class of neurological MRE disorders - bidirectional transcription, intranuclear RNA foci, and repeat associated non-AUG (RAN) translation - which are the subject of this review. Additionally, many MRE disorders share similar underlying molecular pathologies that have been recently targeted in experimental and preclinical contexts. We discuss the therapeutic potential of versatile therapeutic strategies that may selectively target disrupted RNA-based processes and may be readily adaptable for the treatment of multiple MRE disorders. Collectively, the strategies under consideration for treatment of multiple MRE disorders include reducing levels of toxic RNA, preventing RNA foci formation, and eliminating the downstream cellular toxicity associated with peptide repeats produced by RAN translation. While treatments are still lacking for the majority of MRE disorders, several promising therapeutic strategies have emerged and will be evaluated within this review.
...
PMID:Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies. 3317 4
