Table 4.
Role of BDNF in amyotrophic lateral sclerosis.
| Observations | References | |
|---|---|---|
| ALS patients | ||
| The frequency of the CT genotype and the C270T T allele was significantly higher in the ALS group than in the controls. BDNF C270T polymorphism may be a candidate susceptibility locus for sALS, at least in Han Chinese populations. | [116] | |
| The BDNF serum levels did not differ between the patients and the controls, although ∼25% lower levels characterized the patients carrying a depressive trait. The BDNF serum levels were significantly lower in the ALS patients expressing lower cognitive scores. | [117] | |
| The BDNF immunoreactivity was markedly positive in the epidermis and moderately positive in some dermal blood vessels and glands. A metabolic BDNF alteration may take place in the skin of ALS patients. | [118] | |
| Animal model | ||
| Pre- and symptomatic SOD1G93A mice | There are imbalances between (I) BDNF and TrkB isoforms, (II) PKC isoforms and PKA subunits, and (III) Munc18-1 and SNAP-25 phosphorylation ratios in symptomatic mice. Changes in TrkB.T1 and cPKCβI are frequently observed in pre-symptomatic mice. | [121] |
| SOD1G93A T1-/- ALS mouse model | TrkB.T1 deletion significantly delayed the onset of motor-neuron degeneration and the development of muscle weakness. | [122] |
| ALS G93A SOD1 animal model | TrkB.T1 may limit BDNF signaling to motoneurons via a non-cellular autonomous mechanism. | [123] |
| SOD1G93A transgenic mice | Significant improvements in behavioral and electrophysiological results, motoneuron survival, and anti-apoptotic/survival-activated pathways were observed with BDNF-TTC treatment. However, no synergistic effect was found for this fusion molecule. | [129] |
| hSOD1G93A mice | The transplantation of BDNF-overexpressing hUC-MSC-derived motor neurons improves motor performance and prolongs the survival of hSOD1G93A mice. | [131] |
| Cell culture | ||
| NSC-34 cells | The exogenous BDNF supplementation ameliorated most, but not all, degenerative changes. BDNF supplementation reversed autocrine expression; however, it may not be completely receptor-mediated, as the TrkB levels were not restored. BDNF completely revived ChAT expression, inhibited apoptosis, and partially reversed organellar ultrastructural changes. | [130] |