Introduction
TDP-43 and TDP-43 Proteinopathy
TDP-43 Protein Function
TDP-43 Proteinopathy
Disease Mechanisms in the TDP-43 Proteinopathies
Disease Mechanisms Upstream of TDP-43 Proteinopathies
Genetic Factors in ALS
Gene | ALS/FTD | Percentage of cases | TDP-43 deposits | Characteristic features | Refs*
| ||||
---|---|---|---|---|---|---|---|---|---|
ALS | FTD | ||||||||
Sporadic | Familial | Sporadic | Familial | ||||||
Sporadic ALS | ALS | 90–95 | – | – | + | – | – | ||
RNA processing |
C9ORF72
| Both | 4–7 | 39 | 6 | 25 | + | DPRs, RNA foci | [177] |
TARDBP
| Both | 1 | 4 | <1 | + | – | |||
MATR3
| ALS | 1 | 1 | – | + | Matrin 3 elevated/ inclusions | [121] | ||
hnRNPA1
| ALS, MSP | <1 | 2 | – | +†
| hnRNPA1 inclusions†
| [122] | ||
FUS
| Both | 1 | 4 | <1 | – | FUS inclusions | |||
Protein degradation |
UBQLN2
| Both | <1 | <1 | <1 | + | UBQLN2 inclusions | ||
VCP
| Both, MSP | 1 | 1 | <1 | + | Nuclear TDP-43 inclusions | |||
SQSTM1
| ALS, PDB | <1 | 1 | – | + | Increased p62 inclusions | [42] | ||
OPTN
| ALS, POAG | <1 | <1 | – | + | OPTN inclusions | [42] | ||
Other |
SOD1
| ALS | 1–2 | 12 | – | – | SOD-1 inclusions | [42] |