TY  - JOUR
A1  - Franco-Espin, Julio
A1  - Gatius, Alaó
A1  - Armengol, José Ángel
A1  - Arumugam, Saravanan
A1  - Moradi, Mehri
A1  - Sendtner, Michael
A1  - Calderó, Jordi
A1  - Tabares, Lucia
T1  - SMN is physiologically downregulated at wild-type motor nerve terminals but aggregates together with neurofilaments in SMA mouse models
JF  - Biomolecules
N2  - Survival motor neuron (SMN) is an essential and ubiquitously expressed protein that participates in several aspects of RNA metabolism. SMN deficiency causes a devastating motor neuron disease called spinal muscular atrophy (SMA). SMN forms the core of a protein complex localized at the cytoplasm and nuclear gems and that catalyzes spliceosomal snRNP particle synthesis. In cultured motor neurons, SMN is also present in dendrites and axons, and forms part of the ribonucleoprotein transport granules implicated in mRNA trafficking and local translation. Nevertheless, the distribution, regulation, and role of SMN at the axons and presynaptic motor terminals in vivo are still unclear. By using conventional confocal microscopy and STED super-resolution nanoscopy, we found that SMN appears in the form of granules distributed along motor axons at nerve terminals. Our fluorescence in situ hybridization and electron microscopy studies also confirmed the presence of β-actin mRNA, ribosomes, and polysomes in the presynaptic motor terminal, key elements of the protein synthesis machinery involved in local translation in this compartment. SMN granules co-localize with the microtubule-associated protein 1B (MAP1B) and neurofilaments, suggesting that the cytoskeleton participates in transporting and positioning the granules. We also found that, while SMN granules are physiologically downregulated at the presynaptic element during the period of postnatal maturation in wild-type (non-transgenic) mice, they accumulate in areas of neurofilament aggregation in SMA mice, suggesting that the high expression of SMN at the NMJ, together with the cytoskeletal defects, contribute to impairing the bi-directional traffic of proteins and organelles between the axon and the presynaptic terminal.
KW  - spinal muscular atrophy
KW  - motor neuron degeneration
KW  - SMN granules
KW  - neuromuscular junction
KW  - β-actin mRNA
KW  - MAP1B
KW  - neurofilaments
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290263
SN  - 2218-273X
VL  - 12
IS  - 10
ER  - 
TY  - JOUR
A1  - Huss, André
A1  - Abdelhak, Ahmed
A1  - Mayer, Benjamin
A1  - Tumani, Hayrettin
A1  - Müller, Hans-Peter
A1  - Althaus, Katharina
A1  - Kassubek, Jan
A1  - Otto, Markus
A1  - Ludolph, Albert C.
A1  - Yilmazer-Hanke, Deniz
A1  - Neugebauer, Hermann
T1  - Association of serum GFAP with functional and neurocognitive outcome in sporadic small vessel disease
JF  - Biomedicines
N2  - Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In 42 sporadic CSVD patients, we prospectively analysed WMH on magnetic resonance imaging (MRI) and the biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase3-like protein 1 (CHI3L1), Tau and Aβ1-42 in CSF and NfL and GFAP in serum. GFAP and CHI3L1 expression was studied in post-mortem brain tissue in additional cases. CSVD cases with higher serum NfL and GFAP levels had a higher modified Rankin Scale (mRS) and NIHSS score and lower CSF Aβ1-42 levels, whereas the CSF NfL and CHI3L1 levels were positively correlated with the WMH load. Moreover, the serum GFAP levels significantly correlated with the neurocognitive functions. Pathological analyses in CSVD revealed a high density of GFAP-immunoreactive fibrillary astrocytic processes in the periventricular white matter and clusters of CHI3L1-immunoreactive astrocytes in the basal ganglia and thalamus. Thus, besides NfL, serum GFAP is a highly promising fluid biomarker of sporadic CSVD, because it does not only correlate with the clinical severity but also correlates with the cognitive function in patients.
KW  - chitinase-3-like protein 1
KW  - GFAP
KW  - neurofilaments
KW  - white matter hyperintensities
KW  - biomarker
KW  - CSVD
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285973
SN  - 2227-9059
VL  - 10
IS  - 8
ER  -