Table 3 Summary of piRNAs aberrantly expressed in neural processes and diseases

Neural development

172 piRNAs expressed

piRNAs regulate dendritic spine development

Mouse

[5]

Neural development

PIWIL1 protein

PIWIL1 promotes the multipolar morphology to the bipolar transition in cortex neurons

Mouse

[133]

Axonal regeneration

piRNA-like sncRNAs (piLRNAs)

MIWI/piLRNA complex attenuates axonal regeneration in rat sciatic nerve after crush injury

Rat

[134]

Axonal regeneration

3447 piRNAs upregulated, 4117 piRNAs downregulated

MIWI-piRNA complex participates in Schwann cell responses to nerve injury

Mouse

[135]

Axonal regeneration

piRNA pathway

piRNA pathway inhibits axonal regrowth dependent on PIWI protein PRG-1

C. elegans

[13]

Memory formation

Abundant expression of 28-nt piRNAs

Piwi/piRNA complex promotes serotonin-dependent methylation in the CREB2 promoter

Aplysia

[136]

Memory formation

PIWIL1 and PIWIL2

Knockdown of Piwil1 and Piwil2 enhances contextual fear memory

Mouse

[137]

Memory formation

PIWI protein less abundant in αβ mushroom body neurons

Transposon inserts in αβ neurons, including insertion into memory-relevant loci

Drosophila

[138]

Memory formation

piRNAs significantly changed after worm exposure to PA14

PIWI/PRG-1 is required for the induction of daf-7 expression in ASI neurons and induces the nuclear RNAi pathway in the transgenerational inheritance of learned pathogen avoidance behavior

C. elegans

[139, 140]

AD

81 piRNAs upregulated, 22 piRNAs downregulated

piRNAs are nominally correlated with the genome-wide significant risk SNPs

Prefrontal cortex from AD patients

[11]

AD

146 piRNAs upregulated, 3 piRNAs downregulated

piRNA targets focus on the 5 most significant AD-associated pathways enriched with 4 genes regulated by 4 piRNAs

AD patient brain

[12]

AD

Depletion of piRNAs

Depletion of piRNAs would drive transposable element dysregulation that leads to tauopathy neurodegeneration

Drosophila

[15]

PD

piRNAs deregulation

Massive deregulation of piRNAs in neuronal cells

Sporadic PD- derived neuronal cells

[14]

ALS

Aub overexpression

Caz knockdown increases pre-piRNA levels, but reduces mature-size piRNA levels in the central nervous system

Drosophila

[141]

Stroke

54 piRNAs upregulated, 51 piRNAs downregulated

Transcription factors control stroke-responsive piRNAs in a redundant manner

Rat

[142]

Rett Syndrome

piRNAs increased in Mecp2-knockout mouse cerebellum

Upregulated transposons in Rett syndrome may lead to the increase of total piRNAs

Mouse

[143]

Neuropathic

pain

piRNA-DQ541777

piR-DQ541777 recruits DNMT3a to increase methylation of Cdk5rap1 promoter during neuropathic pain

Mouse

[144]

Anxiety

Mili knockout

Knockout of Mili induces LINE1 promoter hypomethylation in mouse brain and reduces anxiety-like behavior

Mouse

[145]