Pathobiological basis of gait dysfunction in Parkinson’s disease

Parkinson’s disease (PD) is classically characterized by degeneration of the substantia nigra with resulting dopaminergic deficiency. Lewy body and Lewy neurite formation as a result of α-synuclein accumulation in cells is the hallmark pathologic marker of PD. 

Gait dysfunction, especially freezing of gait (FOG), remains a challenging problem in PD refractory to medical and surgical therapies.

Lewy-related pathology is present not only in the substantia nigra but also in other important locomotor centers in the brainstem and spinal cord that control gait.

Variability in the distribution of Lewy-related pathology in the brainstem and spinal cord likely is an important factor in the different efficacies of various therapies for gait dysfunction.

Personalized interventions based on specific distribution of Lewy-related pathology and resulting dysfunctional circuits could improve the efficacy of therapies.

https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(25)00016-5

https://sciencemission.com/pathobiological-basis-of-gait-dysfunction-in-PD