Journal: Metabolism Open

Article Title: Non-coding RNAs in neurodegeneration: an axis-based, evidence-tiered mechanistic synthesis

doi: 10.1016/j.metop.2026.100458

Figure Lengend Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Article Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Techniques:

Journal: Metabolism Open

Article Title: Non-coding RNAs in neurodegeneration: an axis-based, evidence-tiered mechanistic synthesis

doi: 10.1016/j.metop.2026.100458

Figure Lengend Snippet: Axis II Neuroinflammation and glia-neuron crosstalk. ( A ) miRNA axis recurrently linked to inflammatory amplification and glial activation, illustrating representative nodes associated with cytokine signaling and microglial state shifts (e.g., miR-155 and pro-inflammatory cytokine outputs; let-7a_STAT3-related signaling; miR-124 as a homeostatic regulator; and miR-195/ROCK1-linked microglial activation). ( B ) lncRNAs positioned as inflammatory “state regulators” through transcriptional and post-transcriptional control, including examples frequently discussed in neurodegenerative inflammatory contexts (e.g., MALAT1 with IL-6/TNF-α profiles; NEAT1/miR-212-3p; and TUG1/miR-152-3p/PTEN signaling). ( C ) circRNA candidates proposed to tune innate immune signaling and glial polarization, highlighting representative axes such as circ_0000518 engaging FUS/CaMKKβ/AMPK pathways and M1 polarization, and circHIPK2 acting via miRNA sequestration with downstream receptor-linked stress responses (e.g., SIGMAR1-related signaling).

Article Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Techniques: Amplification, Activation Assay, Control

Journal: Metabolism Open

Article Title: Non-coding RNAs in neurodegeneration: an axis-based, evidence-tiered mechanistic synthesis

doi: 10.1016/j.metop.2026.100458

Figure Lengend Snippet: Axis IV Mitochondrial stress, oxidative injury, and autophagy-lysosome dynamics. ( A ) miRNA-linked pathways that connect mitochondrial quality control, autophagy regulation, and stress–inflammation coupling, highlighting representative nodes discussed in PD and related neurodegenerative contexts (e.g., miR-124 aligned with autophagy regulation; and miR-195/ROCK1-associated microglial activation as a mechanistic bridge between inflammation and cellular stress). ( B ) lncRNA candidates implicated in proteostasis–mitochondrial crosstalk through ubiquitination and lysosome/autophagy axis, illustrating examples such as lnc-ABCA12-3/UBQLN1-linked ubiquitination/autophagy pathways and lnc-HIBADH-4 miR-326 CTSD axes that converge on lysosomal protease activity and autophagy flux. ( C ) circRNA mediated tuning of mitochondrial homeostasis and mitophagy pathways, highlighting representative ceRNA-like motifs including circEPS15/miR-24-3p/PINK1–PRKN-dependent mitophagy, and circ016719/miR-29c/Map2k6-associated stress survival and apoptosis regulation. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Article Snippet: Axis Proteostasis/homeostasis and pathological protein accumulation. ( A ) Representative miRNA nodes implicated in proteostasis collapse across neurodegenerative settings, highlighting links to amyloidogenic processing and stress signaling (e.g., miR-29/BACE1 in Aβ plaque burden; miR-146a–NF-κB signaling intersecting with tau-related pathology; and ALS-associated vulnerability aligned with impaired miRNA processing such as miR-218 depletion). ( B ) lncRNA-mediated regulation of proteostasis-related gene axis, emphasizing lncRNAs proposed to modulate amyloidogenic pathways and protein handling (e.g., BACE1-AS, NDM29, and 51A/SORL1-related mechanisms), as well as aggregation-relevant nodes reported in PD contexts (e.g., HOTAIR–miR-221-3p–α-synuclein-related phenotypes). ( C ) circRNA-linked regulatory motifs that converge on neuronal injury and proteostasis-adjacent clearance pathways, primarily via miRNA-coupled axes (e.g., circAXL/miR-328/BACE1; circLPAR1/miR-212-3p/ZNF217; and circBptf/miR-138-5p/p62/SQSTM1).

Techniques: Control, Activation Assay, Ubiquitin Proteomics, Activity Assay