ER strikes again: Proteostasis Dysfunction In ALS

The precise contribution of endoplasmic reticulum (ER) chaperone protein disulfide isomerase (PDI) variants in human amyotrophic lateral sclerosis (ALS) patients to the pathogenesis of ALS remained unclear. In the present study, Woehlbier et al (2016) demonstrated that these PDI variants are capable of altering motor neuron morphology, impairing the expression of synaptic proteins, and compromising neuromuscular junction (NMJ) integrity.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Molecular Biology of Disease, Neuroscience News [amp ] Views Source Type: research

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We describe a case of a 33-year-old man with a previous diagnosis of type 3 GD who displayed a progressive weakening of the limbs followed by upper motor neuron involvement. A diagnosis of definite Amyotrophic Lateral Sclerosis was made. This is the first reported case of concurrent Gaucher disease and the ALS phenotype in the same patient.
Source: Molecular Genetics and Metabolism Reports - Category: Genetics & Stem Cells Source Type: research
ConclusionsPLS is associated with considerable subcortical grey matter degeneration and due to the extensive extra-motor involvement, it should no longer be regarded a pure upper motor neuron disorder. Given its unique pathological features and a clinical course which differs considerably from ALS, dedicated research studies and disease-specific therapeutic strategies are urgently required in PLS.
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
CONCLUSIONS: Our study demonstrates that the CST was impaired in both ALS and pLMND patients, thus suggesting that DTI metrics are a reliable tool in detecting subtle changes of UMN in pLMND patients, also in the absence of clinical and CMCT abnormalities. PMID: 31715609 [PubMed - as supplied by publisher]
Source: Neuro-Degenerative Diseases - Category: Neurology Authors: Tags: Neurodegener Dis Source Type: research
Abstract The complement cascade is an important arm of the immune system that plays a key role in protecting the central nervous system (CNS) from infection. Recently, it has also become clear that complement proteins have fundamental roles in the developing and aging CNS that are distinct from their roles in immunity. During neurodevelopment, complement signalling is involved in diverse processes including neural tube closure, neural progenitor proliferation and differentiation, neuronal migration, and synaptic pruning. In acute neurotrauma and ischamic brain injury, complement drives inflammation and neuronal de...
Source: Seminars in Immunology - Category: Allergy & Immunology Authors: Tags: Semin Immunol Source Type: research
ConclusionsThese results show the importance of expressing quality of life in a conceptually appropriate way, as failing to take account of the multidimensional nature of QoL can result in important nuances being overlooked. Clinicians must be aware that pain, depression and anxiety all worsen QoL across their ranges, and not just when pain is severe or when anxiety or depression reach case level.
Source: Journal of Neurology - Category: Neurology Source Type: research
Conclusion: Patient-reported prevalence of NMS in adult SMA was low, which does not argue for a clinically relevant multisystemic disorder in SMAII/III. Importantly, adult SMA patients do not seem to suffer more frequently from symptoms of depression or adaptive disorders compared to controls. Our results yield novel information on previously underreported symptoms and will help to improve the medical guidance of these patients.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
ConclusionsComputational brainstem imaging captures the degeneration of both white and grey matter components in ALS. Our longitudinal data indicate progressive brainstem atrophy over time, underlining the biomarker potential of quantitative brainstem measures in ALS. At a time when a multitude of clinical trials are underway worldwide, there is an unprecedented need for accurate biomarkers to monitor disease progression and detect response to therapy. Brainstem imaging is a promising addition to candidate biomarkers of ALS and PLS.
Source: NeuroImage: Clinical - Category: Radiology Source Type: research
In this study, we have investigated the major molecular factors that mainly contribute to SOD1 destabilization, intrinsic disorder, and misfolding using sequence and structural information. We have analysed 153 ALS causing SOD1 point mutants for aggregation tendency using four different aggregation prediction tools, viz., Aggrescan3D (A3D), CamSol, GAP and Zyggregator. Our results suggest that 74-79 mutants are susceptible to aggregation, due to distorted native interactions originated at the mutation site. Majority of the aggregation prone mutants are located in the buried regions of SOD1 molecule. Further, the mutations ...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research
ConclusionThis review shows that CAM may be useful for ALS treatment, but more evidence regarding the efficacy and molecular mechanisms is required to establish CAM as a good therapy for the treatment of ALS patients.
Source: Integrative Medicine Research - Category: Complementary Medicine Source Type: research
Source: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration - Category: Neurology Authors: Source Type: research
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