scholarly journals Amyotrophic lateral sclerosis, gene deregulation in the anterior horn of the spinal cord and frontal cortex area 8: implications in frontotemporal lobar degeneration

Aging ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 823-851 ◽  
Author(s):  
Pol Andrés-Benito ◽  
Jesús Moreno ◽  
Ester Aso ◽  
Mónica Povedano ◽  
Isidro Ferrer
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Frontal Cortex ◽  
Frontotemporal Lobar Degeneration ◽  
Anterior Horn ◽  
Cortex Area ◽  
Lateral Sclerosis

scholarly journals TDP-43 Vasculopathy in the Spinal Cord in Sporadic Amyotrophic Lateral Sclerosis (sALS) and Frontal Cortex in sALS/FTLD-TDP

2021 ◽  
Vol 80 (3) ◽  
pp. 229-239
Author(s):  
Isidro Ferrer ◽  
Pol Andrés-Benito ◽  
Margarita Carmona ◽  
Abdelilah Assialioui ◽  
Mónica Povedano
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Frontal Cortex ◽  
Blood Vessels ◽  
External Surface ◽  
Sporadic Amyotrophic Lateral Sclerosis ◽  
Double Labeling ◽  
Cortex Area ◽  
Altered Blood ◽  
Lateral Sclerosis

Abstract Sporadic amyotrophic lateral sclerosis (sALS) and FTLD-TDP are neurodegenerative diseases within the spectrum of TDP-43 proteinopathies. Since abnormal blood vessels and altered blood-brain barrier have been described in sALS, we wanted to know whether TDP-43 pathology also occurs in blood vessels in sALS/FTLD-TDP. TDP-43 deposits were identified in association with small blood vessels of the spinal cord in 7 of 14 cases of sALS and in small blood vessels of frontal cortex area 8 in 6 of 11 FTLD-TDP and sALS cases, one of them carrying a GRN mutation. This was achieved using single and double-labeling immunohistochemistry, and double-labeling immunofluorescence and confocal microscopy. In the sALS spinal cord, P-TDP43 Ser403-404 deposits were elongated and parallel to the lumen, whereas others were granular, seldom forming clusters. In the frontal cortex, the inclusions were granular, or elongated and parallel to the lumen, or forming small globules within or in the external surface of the blood vessel wall. Other deposits were localized in the perivascular space. The present findings are in line with previous observations of TDP-43 vasculopathy in a subset of FTLD-TDP cases and identify this pathology in the spinal cord and frontal cortex in a subset of cases within the sALS/FTLD-TDP spectrum.

scholarly journals Extracellular Vesicles in Serum and Central Nervous System Tissues Contain microRNA Signatures in Sporadic Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 14 ◽  
Author(s):  
Ting-wen Lo ◽  
Claudia Figueroa-Romero ◽  
Junguk Hur ◽  
Crystal Pacut ◽  
Evan Stoll ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Amyotrophic Lateral Sclerosis ◽  
Nervous System ◽  
Frontal Cortex ◽  
Extracellular Vesicles ◽  
Long Term Potentiation ◽  
Extracellular Vesicle ◽  
Sporadic Als ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a terminalneurodegenerative disease. Clinical and molecular observations suggest that ALS pathology originates at a single site and spreads in an organized and prion-like manner, possibly driven by extracellular vesicles. Extracellular vesicles (EVs) transfer cargo molecules associated with ALS pathogenesis, such as misfolded and aggregated proteins and dysregulated microRNAs (miRNAs). However, it is poorly understood whether altered levels of circulating extracellular vesicles or their cargo components reflect pathological signatures of the disease. In this study, we used immuno-affinity-based microfluidic technology, electron microscopy, and NanoString miRNA profiling to isolate and characterize extracellular vesicles and their miRNA cargo from frontal cortex, spinal cord, and serum of sporadic ALS (n = 15) and healthy control (n = 16) participants. We found larger extracellular vesicles in ALS spinal cord versus controls and smaller sized vesicles in ALS serum. However, there were no changes in the number of extracellular vesicles between cases and controls across any tissues. Characterization of extracellular vesicle-derived miRNA cargo in ALS compared to controls identified significantly altered miRNA levels in all tissues; miRNAs were reduced in ALS frontal cortex and spinal cord and increased in serum. Two miRNAs were dysregulated in all three tissues: miR-342-3p was increased in ALS, and miR-1254 was reduced in ALS. Additional miRNAs overlapping across two tissues included miR-587, miR-298, miR-4443, and miR-450a-2-3p. Predicted targets and pathways associated with the dysregulated miRNAs across the ALS tissues were associated with common biological pathways altered in neurodegeneration, including axon guidance and long-term potentiation. A predicted target of one identified miRNA (N-deacetylase and N-sulfotransferase 4; NDST4) was likewise dysregulated in an in vitro model of ALS, verifying potential biological relevance. Together, these findings demonstrate that circulating extracellular vesicle miRNA cargo mirror those of the central nervous system disease state in ALS, and thereby offer insight into possible pathogenic factors and diagnostic opportunities.

scholarly journals A 14-3-3 mRNA Is Up-Regulated in Amyotrophic Lateral Sclerosis Spinal Cord

2008 ◽  
Vol 75 (6) ◽  
pp. 2511-2520 ◽  
Author(s):  
Andrea Malaspina ◽  
Narendra Kaushik ◽  
Jackie de Belleroche
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Lateral Sclerosis
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