scholarly journals Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis

2011 ◽  
Vol 69 (1) ◽  
pp. 141-151 ◽  
Author(s):  
Renée Douville ◽  
Jiankai Liu ◽  
Jeffrey Rothstein ◽  
Avindra Nath
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Lateral Sclerosis

scholarly journals TDP-43 and HERV-K Envelope-Specific Immunogenic Epitopes Are Recognized in ALS Patients

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2301
Author(s):  
Elena Rita Simula ◽  
Giannina Arru ◽  
Ignazio Roberto Zarbo ◽  
Paolo Solla ◽  
Leonardo A. Sechi
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Humoral Response ◽  
Dna Binding Protein ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Als Patients ◽  
Circulating Levels ◽  
Lateral Sclerosis

The human endogenous retrovirus-K (HERV-K) and TAR DNA-binding protein 43 (TDP-43) have been associated with the pathophysiology of amyotrophic lateral sclerosis (ALS). Given these findings, we investigated the humoral response against HERV-K envelope surface (env-su) glycoprotein antigens and TDP-43 in the plasma of ALS patients and healthy controls (HCs). The measured levels of Abs against the different epitopes’ fragments were significantly elevated in ALS patients, both in long-survivor (LS) and newly diagnosed (ND) patients, compared to HCs. We observed a positive correlation between HERV-K and TDP-43 antibodies (Abs) levels, which seemed to strengthen with disease progression, that was not found in HCs. The TDP-43 and HERV-K epitopes identified in this study are highly immunogenic and recognized by the humoral response of ALS patients. Increased circulating levels of Abs directed against specific HERV-K- and TDP-43-derived epitopes could serve as possible biomarkers.

scholarly journals A HML6 endogenous retrovirus on chromosome 3 is upregulated in amyotrophic lateral sclerosis motor cortex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashley R. Jones ◽  
Alfredo Iacoangeli ◽  
Brett N. Adey ◽  
Harry Bowles ◽  
Aleksey Shatunov ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Reverse Transcriptase ◽  
Endogenous Retrovirus ◽  
Reverse Transcriptase Activity ◽  
Endogenous Retroviruses ◽  
Post Mortem ◽  
Multiple Testing Correction ◽  
Transcriptase Activity ◽  
Lateral Sclerosis

AbstractThere is increasing evidence that endogenous retroviruses (ERVs) play a significant role in central nervous system diseases, including amyotrophic lateral sclerosis (ALS). Studies of ALS have consistently identified retroviral enzyme reverse transcriptase activity in patients. Evidence indicates that ERVs are the cause of reverse transcriptase activity in ALS, but it is currently unclear whether this is due to a specific ERV locus or a family of ERVs. We employed a combination of bioinformatic methods to identify whether specific ERVs or ERV families are associated with ALS. Using the largest post-mortem RNA-sequence datasets available we selectively identified ERVs that closely resembled full-length proviruses. In the discovery dataset there was one ERV locus (HML6_3p21.31c) that showed significant increased expression in post-mortem motor cortex tissue after multiple-testing correction. Using six replication post-mortem datasets we found HML6_3p21.31c was consistently upregulated in ALS in motor cortex and cerebellum tissue. In addition, HML6_3p21.31c showed significant co-expression with cytokine binding and genes involved in EBV, HTLV-1 and HIV type-1 infections. There were no significant differences in ERV family expression between ALS and controls. Our results support the hypothesis that specific ERV loci are involved in ALS pathology.

Automated Acoustic Analysis of Oral Diadochokinesis to Assess Bulbar Motor Involvement in Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 63 (1) ◽  
pp. 59-73 ◽  
Author(s):  
Panying Rong
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Acoustic Analysis ◽  
Speaking Rate ◽  
Disease Stage ◽  
Healthy Controls ◽  
Tongue Movement ◽  
Major Barrier ◽  
Syllable Repetition ◽  
Oral Diadochokinesis ◽  
Lateral Sclerosis

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.

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