Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IMPORTANCE OF THE FIELD: With the emergence of therapeutic candidates for the incurable and rapidly progressive neurodegenerative condition of amyotrophic lateral sclerosis (ALS), it will be essential to develop easily obtainable biomarkers for diagnosis, as well as monitoring, in a disease where clinical examination remains the predominant diagnostic tool. Magnetic resonance imaging (MRI) has greatly developed over the past thirty years since its initial introduction to neuroscience. With multi-modal applications, MRI is now offering exciting opportunities to develop practical biomarkers in ALS. AREAS COVERED IN THIS REVIEW: The historical application of MRI to the field of ALS, its state-of-the-art and future aspirations will be reviewed. Specifically, the significance and limitations of structural MRI to detect gross morphological tissue changes in relation to clinical presentation will be discussed. The more recent application of diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), functional and resting-state MRI (fMRI & R-fMRI) will be contrasted in relation to these more conventional MRI assessments. Finally, future aspirations will be sketched out in providing a more disease mechanism-based molecular MRI. WHAT THE READER WILL GAIN: This review will equip the reader with an overview of the application of MRI to ALS and illustrate its potential to develop biomarkers. This discussion is exemplified by key studies, demonstrating the strengths and limitations of each modality. The reader will gain an expert opinion on both the current and future developments of MR imaging in ALS. TAKE HOME MESSAGE: MR imaging generates potential diagnostic, prognostic and therapeutic monitoring biomarkers of ALS. The emerging fusion of structural, functional and potentially molecular imaging will improve our understanding of wider cerebral connectivity and holds the promise of biomarkers sensitive to the earliest changes.
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PMID:Advances in the application of MRI to amyotrophic lateral sclerosis. 2151 59

The innate and adaptive immune system plays an important role in diverse forms of central nervous system (CNS) pathologies including neurodegenerative diseases and peripheral nerve injury. Evidence for an innate inflammatory response in Alzheimer's disease (AD) was described 20 years ago, and subsequent studies have documented roles of inflammation in Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and a growing number of other CNS pathologies. Although inflammation may not be the initiating factor for neurodegenerative pathologies, experimental data suggests that persistent inflammatory responses involving microglia and astrocytes, as well as blood monocyte-derived macrophages, clearly contribute to disease progression. High levels of hydrogen sulfide exert toxic effects to CNS. On the other hand, low and physiological levels of H2S may have beneficial effects on number of tissues including CNS. For example, a number of studies have reported that H2S exerts anti-inflammatory and anti-apoptotic effects in CNS. In this chapter, studies related to the role of H2S in neuroinflammation and neurodegeneration will be reviewed and discussed. In particular, we will focus on the role of H2S in neuroinflammation associated with PD.
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PMID:Hydrogen Sulfide and Neuroinflammation. 2616 35

SEE SCABER AND TALBOT DOI101093/AWW264 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: A GGGGCC repeat expansion in C9orf72 leads to frontotemporal dementia and/or amyotrophic lateral sclerosis. Diverse pathological features have been identified, and their disease relevance remains much debated. Here, we describe two illuminating patients with frontotemporal dementia due to the C9orf72 repeat expansion. Case 1 was a 65-year-old female with behavioural variant frontotemporal dementia accompanied by focal degeneration in subgenual anterior cingulate cortex, amygdala, and medial pulvinar thalamus. At autopsy, widespread RNA foci and dipeptide repeat protein inclusions were observed, but TDP-43 pathology was nearly absent, even in degenerating brain regions. Case 2 was a 74-year-old female with atypical frontotemporal dementia-motor neuron disease who underwent temporal lobe resection for epilepsy 5 years prior to her first frontotemporal dementia symptoms. Archival surgical resection tissue contained RNA foci, dipeptide repeat protein inclusions, and loss of nuclear TDP-43 but no TDP-43 inclusions despite florid TDP-43 inclusions at autopsy 8 years after first symptoms. These findings suggest that C9orf72-specific phenomena may impact brain structure and function and emerge before first symptoms and TDP-43 aggregation.
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PMID:Timing and significance of pathological features in C9orf72 expansion-associated frontotemporal dementia. 2791 5