Cytoplasmic TDP-43 accumulation in cells of the adrenal medulla in individuals with or without amyotrophic lateral sclerosis

2014 ◽  
Vol 34 (6) ◽  
pp. 535-540
Author(s):  
Koichi Okamoto ◽  
Masakuni Amari ◽  
Yukio Fujita ◽  
Kouki Makioka ◽  
Toshio Fukuda ◽  
...  
2021 ◽  
Author(s):  
Kyota Yasuda ◽  
Tomonobu M. Watanabe ◽  
Myeong-Gyun Kang ◽  
Jeong Kon Seo ◽  
Hyun-Woo Rhee ◽  
...  

Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) to form granules in cells, leading to pathogenic aggregations that cause neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Proteomics analysis revealed that FUS granules contain valosin-containing protein (VCP), a member of the AAA family ATPase. Confocal microscopy images showed that VCP co-localized in the FUS granules in cells. This study demonstrates that VCP in granules has a two-faced role in FUS granulation: VCP stabilizes de novo FUS granules, while VCP present in the granules for extended periods dissolves them. This VCP function relies on its ATPase activity to consume ATP in granules. VCP stabilizes de novo FUS by reducing intragranular ATP concentrations to a range below the cytosolic concentration. VCP continually consumes ATP during its stay in the granules, which eventually lowers ATP concentrations to a range that destabilizes the granules. VCP, therefore, acts as a timer to limit the residence of FUS granules in cells and thereby prohibits the FUS fibrillization that occurs in persistent granules. VCP ATPase activity plays a role in FUS granule turnover.


PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35413 ◽  
Author(s):  
Kai Y. Soo ◽  
Julie D. Atkin ◽  
Manal Farg ◽  
Adam K. Walker ◽  
Malcolm K. Horne ◽  
...  

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong

Purpose The purpose of this article was to validate a novel acoustic analysis of oral diadochokinesis (DDK) in assessing bulbar motor involvement in amyotrophic lateral sclerosis (ALS). Method An automated acoustic DDK analysis was developed, which filtered out the voice features and extracted the envelope of the acoustic waveform reflecting the temporal pattern of syllable repetitions during an oral DDK task (i.e., repetitions of /tɑ/ at the maximum rate on 1 breath). Cycle-to-cycle temporal variability (cTV) of envelope fluctuations and syllable repetition rate (sylRate) were derived from the envelope and validated against 2 kinematic measures, which are tongue movement jitter (movJitter) and alternating tongue movement rate (AMR) during the DDK task, in 16 individuals with bulbar ALS and 18 healthy controls. After the validation, cTV, sylRate, movJitter, and AMR, along with an established clinical speech measure, that is, speaking rate (SR), were compared in their ability to (a) differentiate individuals with ALS from healthy controls and (b) detect early-stage bulbar declines in ALS. Results cTV and sylRate were significantly correlated with movJitter and AMR, respectively, across individuals with ALS and healthy controls, confirming the validity of the acoustic DDK analysis in extracting the temporal DDK pattern. Among all the acoustic and kinematic DDK measures, cTV showed the highest diagnostic accuracy (i.e., 0.87) with 80% sensitivity and 94% specificity in differentiating individuals with ALS from healthy controls, which outperformed the SR measure. Moreover, cTV showed a large increase during the early disease stage, which preceded the decline of SR. Conclusions This study provided preliminary validation of a novel automated acoustic DDK analysis in extracting a useful measure, namely, cTV, for early detection of bulbar ALS. This analysis overcame a major barrier in the existing acoustic DDK analysis, which is continuous voicing between syllables that interferes with syllable structures. This approach has potential clinical applications as a novel bulbar assessment.


2019 ◽  
Author(s):  
Naile Alankaya ◽  
Zeliha Tülek ◽  
Aylin Özakgül ◽  
Alper Kaya ◽  
Aynur Dik

2019 ◽  
Author(s):  
Naile Alankaya ◽  
Zeliha Tülek ◽  
Aylin Özakgül ◽  
Alper Kaya ◽  
Aynur Dik

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