Abstract: Disclosed are compositions and methods for inhibiting abnormal protein accumulation, promoting motor neuron survival, inhibiting motor neuron degeneration and treating neurodegenerative conditions through expression of a nucleic acid sequence encoding cyclin F in motor neurons with an abnormally low level or activity of cyclin F. Also disclosed are methods for identifying agents that promote survival of motor neurons, inhibit degeneration of motor neurons and/or inhibit abnormal protein accumulation in motor neurons, identifying agents that are useful for treating neurodegenerative conditions, diagnosing neurodegenerative conditions, predicting the progression of neurodegenerative conditions, and monitoring the effectiveness of a therapy in reducing the progression of a neurodegenerative condition.

Abstract: Provided herein are modified cyclin F polypeptides and nucleic acid molecules encoding the same. In particular, provided herein are modified cyclin F polypeptides that have increased cytoplasmic targeting compared to wild-type cyclin F polypeptides, and functional, truncated modified cyclin F polypeptides, and nucleic acid molecules encoding the same. Also provided herein is the use of the modified cyclin F polypeptides and encoding nucleic acid molecules for enhancing motor neuron survival, inhibiting motor neuron degeneration and treating neurodegenerative conditions, in particular those associated with neuronal TDP-43 proteinopathy.

Abstract: Provided herein are methods for enhancing survival of a neuron, for inhibiting degeneration of a neuron, and for inhibiting abnormal protein accumulation in a neuron, optionally a motor neuron, comprising, consisting or consisting essentially of increasing the level of cyclin F in the neuron regardless of the neuron's level or activity of endogenous cyclin F. Optionally the neuron is in a subject with a neurodegenerative condition or at risk of developing a neurodegenerative condition, typically a neurodegenerative condition associated with a neuronal TDP-43 proteinopathy.

Abstract: Disclosed are compositions and methods for inhibiting abnormal protein accumulation, promoting motor neuron survival, inhibiting motor neuron degeneration and treating neurodegenerative conditions through expression of a nucleic acid sequence encoding cyclin F in motor neurons with an abnormally low level or activity of cyclin F. Also disclosed are methods for identifying agents that promote survival of motor neurons, inhibit degeneration of motor neurons and/or inhibit abnormal protein accumulation in motor neurons, identifying agents that are useful for treating neurodegenerative conditions, diagnosing neurodegenerative conditions, predicting the progression of neurodegenerative conditions, and monitoring the effectiveness of a therapy in reducing the progression of a neurodegenerative condition.