Virus-mediated delivery of single-chain antibody targeting TDP-43 protects against neuropathology, cognitive impairment and motor deficit caused by chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion induced by permanent unilateral common carotid artery occlusion in mice was recently found to induce an age-dependent formation of insoluble cytoplasmic TDP-43 aggregates reminiscent of pathological changes found in human vascular dementia. In this model, the gradual deregulation of TDP-43 homeostasis in cortical neurons was associated with marked cognitive and motor deficits. To target the TDP-43-mediated toxicity in this model, we generated an adeno-associated virus vector encoding a single-chain antibody against TDP-43, called scFv-E6, designed for pan-neuronal transduction following intravenous administration.

Spinal Cord Stimulation for Low Back Pain: A Systematic Review.

Purpose Of Review: Chronic low back pain (LBP) is a prevalent and debilitating condition affecting millions worldwide. Among emerging interventions, spinal cord stimulation (SCS) has gained attention as a potential alternative for managing chronic LBP, particularly when alternative approaches fail to provide adequate relief.

Recent Findings: This systematic review focuses on both residual pain levels and ability to perform daily tasks after treatment with SCS.

Monte Carlo study of organ doses and related secondary cancer risk estimations for patients undergoing prostate radiotherapy: Algerian population-based study.

The present study aimed to assess organ doses and the associated cancer risks related to secondary radiation (photons and neutrons) exposure during 3D Conformational Radiotherapy (3D-CRT) for patients with prostate cancer in Algeria. To this purpose, a detailed geometric Monte Carlo (MC) modeling of the LINAC, combined with a hybrid whole-body phantom was carried out. The secondary radiation doses were calculated in patient's organs, both within and outside the field.

N-Terminal Fragments of TDP-43-In Vitro Analysis and Implication in the Pathophysiology of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration.

Abnormal cytoplasmic aggregates containing the TDP-43 protein and its fragments are present in the central nervous system of the majority of patients with amyotrophic lateral sclerosis (ALS) and in patients with frontotemporal lobar degeneration (FTLD). Many studies have focused on the C-terminal cleavage products of TDP-43 (CTFs), but few have focused on the N-terminal products (NTFs), yet several works and their protein domain composition support the involvement of NTFs in pathophysiology. In the present study, we expressed six NTFs of TDP-43, normally generated in vivo by proteases or following the presence of pathogenic genetic truncating variants, in HEK-293T cells.