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Volume 15
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Review

Redefining Non-Motor Symptoms in Parkinson’s Disease

by
Laura Peña-Zelayeta
1,†,
Karen M. Delgado-Minjares
2,3,†,
Marcos M. Villegas-Rojas
2,4,
Karen León-Arcia
2,5,6,
Alberto Santiago-Balmaseda
2,
Jesús Andrade-Guerrero
2,5,
Isaac Pérez-Segura
2,
Emmanuel Ortega-Robles
1,
Luis O. Soto-Rojas
2,*,† and
Oscar Arias-Carrión
1,7,*,†
1
Unidad de Trastornos del Movimiento y Sueño, Hospital General Dr. Manuel Gea González, Ciudad de México 14080, Mexico
2
Laboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
3
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 07360, Mexico
4
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México 11340, Mexico
5
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico
6
Posgrado en Ciencias Biológicas, Unidad de Posgrado, Edificio A, 1° Piso, Circuito de Posgrados, Ciudad Universitaria, Coyoacán 04510, Mexico
7
Experimental Neurology, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Pers. Med. 2025, 15(5), 172; https://doi.org/10.3390/jpm15050172 (registering DOI)
Submission received: 18 March 2025 / Revised: 23 April 2025 / Accepted: 24 April 2025 / Published: 26 April 2025
(This article belongs to the Special Issue Neurodegenerative Diseases: Molecular Pathology and Personalized Treatment)
Versions Notes

Abstract

Parkinson’s disease involves widespread neurodegeneration that extends far beyond the basal ganglia, giving rise to a diverse range of non-motor symptoms that frequently emerge before motor onset. These include autonomic dysfunction, cognitive decline, neuropsychiatric disturbances, sleep-related disorders, and sensory deficits. Here, we synthesize current evidence on the anatomical, neurochemical, and network-level mechanisms that drive these symptoms, and we examine how they shape disease progression and clinical heterogeneity. We highlight the limitations of dopamine-centric models and advocate for a framework that treats non-motor symptoms as the disorder’s primary, mechanistically distinct features. We also discuss how emerging technologies—such as multi-omic profiling, artificial intelligence, and network neuroscience—enable earlier identification, stratification of non-motor phenotypes, and the development of precision-based therapeutic strategies. Recognizing non-motor symptoms as central to Parkinson’s disease redefines how the disorder should be diagnosed, studied, and treated.
Keywords: Parkinson’s disease; non-motor symptoms; sensory dysfunction; sleep-related disorders; neuropsychiatric disorders; autonomic dysfunction; REM sleep behavior disorder; pain; cognitive impairment; biomarkers Parkinson’s disease; non-motor symptoms; sensory dysfunction; sleep-related disorders; neuropsychiatric disorders; autonomic dysfunction; REM sleep behavior disorder; pain; cognitive impairment; biomarkers

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MDPI and ACS Style

Peña-Zelayeta, L.; Delgado-Minjares, K.M.; Villegas-Rojas, M.M.; León-Arcia, K.; Santiago-Balmaseda, A.; Andrade-Guerrero, J.; Pérez-Segura, I.; Ortega-Robles, E.; Soto-Rojas, L.O.; Arias-Carrión, O. Redefining Non-Motor Symptoms in Parkinson’s Disease. J. Pers. Med. 2025, 15, 172. https://doi.org/10.3390/jpm15050172

AMA Style

Peña-Zelayeta L, Delgado-Minjares KM, Villegas-Rojas MM, León-Arcia K, Santiago-Balmaseda A, Andrade-Guerrero J, Pérez-Segura I, Ortega-Robles E, Soto-Rojas LO, Arias-Carrión O. Redefining Non-Motor Symptoms in Parkinson’s Disease. Journal of Personalized Medicine. 2025; 15(5):172. https://doi.org/10.3390/jpm15050172

Chicago/Turabian Style

Peña-Zelayeta, Laura, Karen M. Delgado-Minjares, Marcos M. Villegas-Rojas, Karen León-Arcia, Alberto Santiago-Balmaseda, Jesús Andrade-Guerrero, Isaac Pérez-Segura, Emmanuel Ortega-Robles, Luis O. Soto-Rojas, and Oscar Arias-Carrión. 2025. "Redefining Non-Motor Symptoms in Parkinson’s Disease" Journal of Personalized Medicine 15, no. 5: 172. https://doi.org/10.3390/jpm15050172

APA Style

Peña-Zelayeta, L., Delgado-Minjares, K. M., Villegas-Rojas, M. M., León-Arcia, K., Santiago-Balmaseda, A., Andrade-Guerrero, J., Pérez-Segura, I., Ortega-Robles, E., Soto-Rojas, L. O., & Arias-Carrión, O. (2025). Redefining Non-Motor Symptoms in Parkinson’s Disease. Journal of Personalized Medicine, 15(5), 172. https://doi.org/10.3390/jpm15050172

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