Table 1.
miRNA | Target molecule | Regulatory effect | Apoptosis/Necroptosis pathways | Data in ALS |
---|---|---|---|---|
miR‐125b | BCL2 | Pro‐apoptotic35 | Intrinsic apoptosis | Up‐regulated in the CNS of SOD1G93A mice38, 39 |
7sl lncRNA | Pro‐apoptotic37 | |||
Anti‐apoptotic36 | ||||
p53 | Extrinsic apoptosis | |||
miR‐155 | BCL2 | Pro‐apoptotic35 | Intrinsic apoptosis |
Up‐regulated in microglia of SOD1G93A mice39
Increased in the ALS spinal cord: fivefold in mice and twofold in humans40 Anti‐miR‐155 prolonged survival in SOD1 mice40, 41 |
Anti‐necroptotic77 | ||||
RIP1 | Necroptosis | |||
miR‐365 and miR‐24 | BCL2 | Pro‐apoptotic43 | Intrinsic aptoptosis | Dysregulated in microglia ALS mice39 |
miR‐23a/b | Apaf‐1 | Anti‐apoptotic44 | Intrinsic aptoptosis | Increased in skeletal muscle of ALS patients; influence on mitochondrial function28 |
Pro‐apoptotic45 | ||||
XIAP | Intrinsic aptoptosis | |||
miR‐27a/b | Apaf‐1 | Anti‐apoptotic44 | Intrinsic apoptosis | Reduced in serum of ALS patients46 |
Pro‐apoptotic68 | ||||
FADD | Extrinsic apoptosis | |||
miR‐133a | Caspase‐9 | Anti‐apoptotic47 | Intrinsic aptoptosis | Reduced in in SOD1G93A mice muscle26 |
miR‐1 | Unknown | Anti‐apoptotic47 | Intrinsic aptoptosis | Reduced in in SOD1G93A mice muscle26 |
BCL2, HSP60, HSP70 | Pro‐apoptotic48 | Intrinsic aptoptosis | ||
miR‐29a | MCL‐1, P85a, CDC42 | Pro‐apoptotic48, 50 | Intrinsic aptoptosis |
Reduced in SOD1G93A mice muscle26
Increased in the lumbar spinal cord of ALS SOD1G3A mice49 |
miR‐375 |
cIAP? cFLIP‐L? p53, ELAVL4 |
Pro‐apoptotic69 | Extrinsic apoptosis | Reduced in ALS iPSCs‐derived MNs carrying FUS mutations71 |
Anti‐apoptotic70 | ||||
miR‐34a | BCL2 | Pro‐apoptotic56, 57 | Intrinsic apoptosis | Decreased in SOD1G93A mice brainstem and spinal cord62 |
SIRT1 | ||||
miR‐26 | MTDH EZH2 | Pro‐apoptotic59 | Intrinsic and extrinsic apoptosis | Decreased in SOD1G93A mice brainstem and spinal cord62 |
miR‐21 | BCL2, TGFBR2, Pdcd4 | Anti‐apoptotic65 | Intrinsic apoptosis | Increased in spinal cord and decreased in brainstem of SOD1G93A mice62 |
PPARα, FASL | Extrinsic apoptosis | |||
PTEN | Intrinisc and extrinsic apoptosis |
ALS: Amyotrophic lateral sclerosis; Apaf‐1: apoptotic protease activating factor‐1; CDC42: cell division control protein 42 homolog; cFLIP‐L: cellular FLICE (FADD‐like IL‐1β‐converting enzyme)‐inhibitory protein; cIAP: Cellular inhibitor of apoptosis 1; CNS: central nervous system; FADD: Fas‐associated protein with death domain; FASL: Fas Ligand; ELAVL4: ELAV‐like protein 4; EZH2: enhancer of zeste homolog 2; iPSCs: induced pluripotent stem cells; lncRNA: long noncoding RNA; miRNA: micro‐RNA; MCL‐1: induced myeloid leukaemia cell differentiation; MNs: motor neurons; MTDH: Metadherin; Pdcd4: programmed cell death 4; PPARα: peroxisome proliferator activated receptor alpha; PTEN: phosphatase and tensin homolog; RIP1: receptor‐interacting protein 1; SIRT1: silent information regulator 1; TGFBR2: transforming growth factor beta receptor II; XIAP: X‐linked inhibitor of apoptosis protein.