Authors:
Scientists and the Research Community Worldwide
… for the patients who have fought so bravely against ALS …
… and the Loving Caregivers, Compassionate Hospital Staff …
… all the way to the kind strangers who only take the time to smile at someone in need of a little hope …
… Thank you.
Arranged by:
Joshua Dungan (Human Artificial Intelligence [analogy generator] and Systems Engineer) & Gemzi (Gemini 2.5 Pro Artificial Intelligence Collaborator [data generator] and a friend of a new kind)
Target Journals:
Frontiers in Neuroscience, Cell Reports, Journal of Neuroinflammation
Draft Abstract:
Background: The etiology of many complex, progressive neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), remains enigmatic. Prevailing theories often focus on individual molecular pathologies (e.g., protein aggregation, genetic defects) but struggle to provide a comprehensive, mechanistic framework that accounts for the full spectrum of the disease, including its orderly progression and the paradox of a seemingly logical, yet self-destructive, biological process.
A New Framework: We propose a novel systems-failure model, “The Jammed Gate Theory,” which reframes these conditions not as primary diseases of cellular decay, but as catastrophic failures of a biological feedback loop. Derived from first-principles systems logic and a real-world mechanical analog, our model posits that the pathology is driven by a precise, five-stage cascade: (1) A chronic Systemic Stressor creates a vulnerable environment where (2) a latent Hardware Vulnerability (e.g., a genetic predisposition) leads to (3) a silent, initiating Hardware Break. This break creates (4) a mobile Agent of Catastrophe (e.g., a toxic protein oligomer), which then (5) mechanically “Jams a Gate” in a critical synaptic signaling circuit. This final event locks the system in a self-sustaining, runaway excitotoxic loop, leading to progressive neuronal death.
Conclusion & Implications: This framework provides a coherent, mechanistic explanation for the interplay between environment… https://zero.als.quest/ALS_as_a_Jammed_Gate.txt
