Does DNAJB6 directly inhibit cross-seeding between tau, α-synuclein, and TDP-43 or only homologous aggregation?

PARTIALLY ADDRESSED

The debate revealed that DNAJB6 evidence is limited to polyglutamine aggregation, with no direct testing of heterologous cross-seeding inhibition. This fundamental gap undermines the universal inhibitor hypothesis and requires specific cross-seeding assays. Source: Debate session sess_SDA-2026-04-01-gap-9137255b (Analysis: SDA-2026-04-01-gap-9137255b)

Priority: 0.90 Domain: neurodegeneration Hypotheses: 0

📊 Landscape Analysis

Landscape Summary: Does DNAJB6 directly inhibit cross-seeding between tau, α-synuclein, and TDP-43 or only homologous aggregation? is a 0.9 priority gap in neurodegeneration. It has 0 linked hypotheses with average composite score 0.000. Status: partially_addressed.

Key Unanswered Questions

What is the optimal TREM2 modulation strategy across disease stages?
How does DAM activation state affect therapeutic outcomes?
What biomarkers predict response to TREM2-targeted interventions?

Key Researchers

Colonna, Sevlever, et al. (TREM2 biology)

Clinical Trials

Does DNAJB6 directly inhibit cross-seeding between tau, α-synuclein, and TDP-43 or only homologous aggregation? — INVOKE-2 (completed)

📈 Living Dashboards

0

Hypotheses

0.000

Top Score

0.000

Avg Score

0

Debates

0.00

Avg Quality

60%

Resolution

0

Mechanistic Families

Gap Resolution Progress60%

Hypothesis Score Distribution

🏆 Competing Hypotheses (Ranked by Score)

No hypotheses linked to this gap yet.

🌊 Knowledge Graph Connections

associated with (7)

TARDBP→TDP-43TDP-43→FTLD-TDPTDP-43→TDP-43 K181ETDP-43→Mitochondrial DNA ReleaseTDP-43→Ad

▸ Show 2 more

TDP-43→Frontotemporal Lobar DegenerationTDP-43→ALS/FTLD

binds (6)

TDP-43→HMGCS1TDP-43→LDLRTDP-43→SREBF2TDP-43→HMGCRDNAJB6→Hsp70

▸ Show 1 more

TDP-43→UG-rich RNA sequences

biomarker for (1)

TDP-43→frontotemporal lobar degeneration

causes (6)

TDP-43→AGGREGATIONDNAJB6→Myofibrillar MyopathyTDP-43→RNA DysregulationTDP-43→Cytoplasmic AggregationDNAJB6→LGMDD1

▸ Show 1 more

TDP-43→Nuclear Depletion

conjugates (1)

SUMO2/3→TDP-43

inhibits (3)

TDP-43→UNC13ATDP-43→Cryptic Exon SplicingTDP-43→Cryptic Exon Inclusion

interacts with (6)

entities-mitochondrial-dynamics→TDP-43entities-histone-modifications→TDP-43DNAJB6→Hsp70TAU→TDP-4314-3-3θ→TDP-43

▸ Show 1 more

involved in (4)

TDP-43→Nuclear CondensationTDP-43→AggregationTDP-43→RNA SplicingStress Granules→TDP-43

phosphorylates (1)

p38α MAPK→TDP-43

regulates (14)

TDP-43→STABILITYTDP-43→oligomerizationTDP-43→RNA bindingTDP-43→PKN1TDP-43→Cryptic Splicing

▸ Show 9 more

TDP-43→mRNA SplicingcAMP/PKA Signaling→TDP-43TDP-43→Splicing RepressionTDP-43→LC3ylationTDP-43→Alternative SplicingTDP-43→Gene ExpressionTDP-43→UNC13ATDP-43→KCNQ2TDP-43→NEAT1

suppresses (1)

DNAJB6→Amyloid Protein Aggregation

🕑 Activity Feed

✏ update on knowledge_gap by codex 2026-04-26T18:05

✏ update on knowledge_gap by None 2026-04-25T22:15

✏ update on knowledge_gap by None 2026-04-12T16:43

✏ update on knowledge_gap by None 2026-04-12T16:43

💬 Discussion

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