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235. Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins
Article type: Literature Review
Article title: Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins
Journal: Journal of Central Nervous System Disease
Year: 2026
Authors: Jamir Pitton Rissardo, Megan Katz, Vishnu Vardhan Byroju, Ana Letícia Fornari Caprara, and Ian M. Walker
E-mail: jamirrissardo@gmail.com
ABSTRACT
Parkinson’s disease (PD) is a rapidly growing global health challenge, with prevalence projected to reach 13–14 million cases by 2040. While aging and improved diagnostic awareness partly explain this trend, mounting evidence implicates environmental factors as critical contributors. This review synthesizes current literature on exposures such as pesticides, solvents, heavy metals, air pollutants, and infectious agents, emphasizing their mechanistic links to neurodegeneration. These factors interact with genetic susceptibility and aging, supporting the “multiple-hit” hypothesis, which posits that PD arises from cumulative insults rather than a single cause. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein clearance emerge as convergent pathways underlying dopaminergic vulnerability. Recent findings highlight viral infections—particularly SARS-CoV-2—as potential triggers or amplifiers of PD pathogenesis, raising concerns about long-term neurological sequelae following pandemics. Beyond individual toxins, the exposome concept underscores the lifelong interplay of physical, chemical, and social exposures in shaping disease risk. Climate-related changes, including increased air pollution and wildfire frequency, further compound these risks, suggesting a systemic dimension to PD etiology. Understanding these complex interactions is essential for developing preventive strategies, refining experimental models, and informing public health policies aimed at mitigating environmental contributions to neurodegeneration. This multifactorial perspective offers a foundation for future research targeting modifiable risk factors and resilience mechanisms in PD.
Keywords: Parkinson’s disease, neurodegeneration, environmental toxins, pesticides, air pollution, heavy metals, solvents, multiple-hithypothesis, SARS-CoV-2, exposome
Full text available at:
DOI
Citation
Pitton Rissardo J, Katz M, Byroju VV, Fornari Caprara AL, Walker IM. Neurodegeneration in Parkinson’s Disease: The Role of Environmental Toxins. Journal of Central Nervous System Disease. 2026;18. doi:10.1177/11795735261461554.
Figure 1. Likelihood of diagnosing Parkinson’s Disease (PD). The probability of a PD diagnosis increases as the cumulative burden of risk factors rises. Key contributors include aging, chronic inflammation, and exposure to environmental toxins and pollutants. These factors interact with genetic susceptibility—particularly high-penetrance mutations—to elevate disease risk. The synergistic effect of these elements underscores the multifactorial nature of PD pathogenesis.
Figure 2. Role of exposome in Parkinson’s Disease. Exposure to environmental factors through an individual’s life-time plays a role in pathogenesis of Parkinson’s disease. (A) Heavy metals (Iron, Zinc, Mercury, Lead, Copper) exposure through paint, tools and drinking water. (B) Air pollution and environmental toxins containing PM2.5, NO2, O3 and other particles. (C) Pesticide and fungicide exposure to 2,4-dichlorodiphenyldichloroethylene, Rotenone, diquat, paraquat and others. (D) Helicobacter pylori infection and other gut microbiomes exert influence. (E) Exercise and physical activity. (F) Exposure to nicotine, intravenous drugs and toxins such as MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). (G) Diet and understanding of macro and micronutrients.
Table 1. Environmental and Biological Risk Factors Associated With Parkinson’s Disease.
Table 2. Toxic Models of Parkinson’s Disease.
Functional Movement Disorders (Part 4): Functional Slowness, Speech and Voice Disorders
Functional Movement Disorders (Part 4): Functional Slowness, Speech and Voice Disorders
Functional Parkinsonism
Video 15.54 (C15c54): Functional Bradykinesia
Apparent slowness without decrement, rigidity, or gait abnormality.
Video 15.55 (C15c55): Functional Reduced Arm Swing
Absent arm swing despite preserved dexterity and normal motor testing.
Video 15.56 (C15c56): Functional Parkinsonism
Effortful movements, variable slowness, distractible involuntary tapping, and collapses inconsistent with organic parkinsonism.
Functional Voice Disorders
Video 15.57 (C15c57): Functional Breathing and Voice Disorder
Paroxysmal stridor, dyspnea, and vocal dysfunction triggered during examination.
Video 15.58 (C15c58): Functional Speech Disorder
Inconsistent low-pitched speech with intrusive consonant production.
Video 15.59 (C15c59): Functional Voice Tremor/Spasm
Neck and vocal intrusions during speech disappearing with altered speaking patterns and singing.
Functional Movement Disorders (Part 3): Functional Spasms, Posturing and Functional Dystonia
Functional Movement Disorders (Part 3): Functional Spasms, Posturing and Functional Dystonia
Functional Spasms and Functional Dystonia
Video 15.34 (C15c34): Functional Spasm Episode
Severe episodic posturing, breathing difficulty, and impaired ambulation.
Video 15.35 (C15c35): Functional Generalized Spasm
Sustained limb and facial posturing with retained interaction during the episode.
Video 15.36 (C15c36): Functional Dystonic Attacks
Stress-related painful sustained posturing with preserved awareness.
Video 15.37 (C15c37): Functional Generalized Dystonia
Continuous complex posturing involving all four limbs.
Video 15.38 (C15c38): Functional Paroxysmal Limb Posturing
Episodic arm dystonia evolving from tremor-like movements.
Video 15.39 (C15c39): Functional Painful Hand Posturing
Jerking hand movements relieved by dramatic flinging behaviors.
Video 15.40 (C15c40): Functional Mixed Hyperkinetic Syndrome
Combination of leg bouncing, arm jerks, facial movements, and neck turning.
Video 15.41 (C15c41): Functional Fixed Finger Flexion
Fixed finger postures resistant to passive manipulation.
Video 15.42 (C15c42): Functional Fixed Dystonia of the Hand
Persistent flexed finger posture with immediate recurrence after correction.
Video 15.43 (C15c43): Functional Dystonia with Jerks
Alternating sustained postures and jerking forearm movements.
Video 15.44 (C15c44): Functional Dystonic Attack
Progression from finger tremor to whole-arm, neck, and trunk involvement.
Video 15.45 (C15c45): Functional Limb Posturing with Gait Impairment
Task-induced arm posturing and nonphysiologic lower-limb dysfunction.
Video 15.46 (C15c46): Functional Facial Spasms
Difficulty closing eyes during attacks with atypical facial contractions.
Video 15.47 (C15c47): Mild Functional Jaw Movement Disorder
Essentially normal examination except intermittent jaw movements.
Video 15.48 (C15c48): Functional Cranio-Cervical Spasms
Repetitive jaw opening, eye closure, facial pulling, and neck flexion.
Video 15.49 (C15c49): Functional Eye Closure Episode
Eye closure with eyebrow elevation and nonanatomic ocular findings.
Video 15.50 (C15c50): Functional Arm Posturing
Jerky arm movements with preference for sustained flexed posture.
Video 15.51 (C15c51): Functional Foot Dystonia
Persistent inversion and adduction posture with inconsistent weakness.
Video 15.52 (C15c52): Functional Upper-Limb Dystonia
Sustained finger and arm flexion despite preserved target-directed movements.
Video 15.53 (C15c53): Functional Gait Disorder with Leg Buckling
Inconsistent lower-limb dysfunction persisting across different gait tasks.
Functional Movement Disorders (Part 2): Functional Tremor, Shaking and Functional Gait Disorders
Functional Movement Disorders (Part 2): Functional Tremor, Shaking and Functional Gait Disorders
Functional Tremor
Video 15.12 (C15c12): Functional Gait Disorder with Shaking
Astasia-abasia and truncal flexion occurring only during standing and walking.
Video 15.13 (C15c13): Functional Cervical Tremor
Variable neck shaking with astasia-abasia gait and nonphysiologic spiral findings.
Video 15.14 (C15c14): Functional Generalized Shaking
Variable-amplitude shaking affecting limbs and trunk with dramatic gait impairment.
Video 15.15 (C15c15): Functional Leg Shaking
Continuous leg shaking accompanied by relative indifference and preserved coordination.
Video 15.16 (C15c16): Functional Gait Disorder
Highly unusual gait with excessive stepping, pelvic tilting, and preserved tandem abilities.
Video 15.17 (C15c17): Functional Leg Tremor
Variable bilateral leg shaking with knee-knocking and astasia-abasia features.
Video 15.18 (C15c18): Functional Upper-Limb Tremor
Complex variable tremor with preserved finger-to-nose accuracy and inconsistent disability.
Video 15.19 (C15c19): Functional Head and Truncal Tremor
Continuous head movements relieved by turning the head and accompanied by gait bouncing.
Video 15.20 (C15c20): Functional Gait and Tremor Syndrome
Bouncing gait, give-way weakness, and prominent astasia-abasia.
Video 15.21 (C15c21): Generalized Functional Tremor
Variable whole-body shaking with differing phenomenology during sitting versus standing.
Video 15.22 (C15c22): Distractible Functional Tremor
Body shaking improving with motor entrainment and distraction.
Video 15.23 (C15c23): Functional Tremor with Speech Disturbance
Arm shaking and speech changes provoked by simple motor tasks.
Video 15.24 (C15c24): Functional Arm Tremor
Tremor during action without impairment of target accuracy.
Video 15.25 (C15c25): Functional Monomelic Tremor
Persistent unilateral arm tremor with inconsistent neurologic findings.
Video 15.26 (C15c26): Entrainable Functional Tremor
Bilateral arm tremor suppressed by contralateral motor tasks.
Video 15.27 (C15c27): Functional Generalized Shaking
Whole-body shaking relieved by purposeful movements and targeting tasks.
Video 15.28 (C15c28): Functional Tremor Mimicking Parkinson Disease
Rest, postural, and action tremor lacking characteristic Parkinsonian features.
Video 15.29 (C15c29): Functional Facial Pulling and Tremor
Facial asymmetry, truncal flexion movements, belching, and task-dependent tremor.
Video 15.30 (C15c30): Functional Generalized Tremor
Continuous variable shaking with spontaneous imbalance and astasia-abasia.
Video 15.31 (C15c31): Distractible Functional Tremor
Latency-dependent hand tremor abolished by cognitive distraction.
Video 15.32 (C15c32): Functional Rest Tremor with Gait Disorder
Variable unilateral tremor and incongruent leg-dragging gait.
Video 15.33 (C15c33): Functional Bilateral Tremor
Asynchronous rest tremor with variable suppression and nonphysiologic spiral performance.
Functional Movement Disorders (Part 1): Functional Jerks and Functional Myoclonus
Functional Movement Disorders (Part 1): Functional Jerks and Functional Myoclonus
Functional Jerks
Video 15.1 (C15c1): Functional Generalized Jerks
Variable jerking movements of the head, trunk, pelvis, and right hand with gait-triggered tremulousness.
Video 15.2 (C15c2): Functional Facial and Cervical Jerks
Variable neck jerks associated with downward eyebrow and mouth pulling.
Video 15.3 (C15c3): Functional Whole-Body Jerks
Continuous jerking of the trunk, head, arms, and legs exacerbated by standing and writing.
Video 15.4 (C15c4): Functional Jerks with Astasia-Abasia
Jerks suppressed by mental distraction and accompanied by highly incongruent gait impairment.
Video 15.5 (C15c5): Functional Multifocal Jerks
Asynchronous limb and truncal jerks with tremulous, pseudo-asterixis-like movements.
Video 15.6 (C15c6): Functional Propriospinal-Like Jerks
Generalized body jerks mimicking propriospinal myoclonus but demonstrating preparatory movements and nonphysiologic spread.
Video 15.7 (C15c7): Functional Hyperkinetic Movement Disorder
Continuous twisting, posturing, clapping, and inability to remain still in the context of psychosocial stress.
Video 15.8 (C15c8): Functional Violent Whole-Body Jerks
Frequent generalized violent jerks involving neck, trunk, arms, and vocalization.
Video 15.9 (C15c9): Functional Jerks with Distractibility
Small-amplitude hand jerks evolving into dramatic bilateral arm jerks responsive to distraction.
Video 15.10 (C15c10): Functional Tremor and Jerks
Distractible intermittent jerks and tremor paradoxically improving during challenging tasks.
Video 15.11 (C15c11): Functional Jerking Episode with Convergence Spasm
Paroxysmal violent flailing movements followed by convergence spasm.
Ataxia Phenomenology Atlas (Part 4): Acquired Cerebellar Syndromes and Nystagmus Disorders
Ataxia Phenomenology Atlas (Part 4): Acquired Cerebellar Syndromes and Nystagmus Disorders
Acquired Cerebellar and Brainstem Disorders
Video 13.60 (C13c60): Multiple Sclerosis with Cerebellar Tremor
Bilateral wing-beating tremor, dysmetria, and titubation.
Video 13.61 (C13c61): Midbrain Hemorrhage with Oculopalatal/Cerebellar Tremor Syndrome
Continuous head tremor, oscillopsia, adduction deficits, and limb cerebellar tremor.
Video 13.62 (C13c62): Lateral Medullary (Wallenberg) Syndrome
Ipsilateral Horner syndrome, limb ataxia, body lateropulsion, and palatal weakness.
Video 13.63 (C13c63): Periodic Alternating Nystagmus from Chiari I Malformation
Alternating direction-changing nystagmus with mild cerebellar syndrome.
Video 13.64 (C13c64): Superficial Siderosis
Severe sensory-vestibular ataxia with marked dependence on visual input.
Video 13.65 (C13c65): Post-Chemotherapy Cerebellar Toxicity
Mild pediatric cerebellar syndrome with subtle gait ataxia.
Video 13.66 (C13c66): Carbamazepine Toxicity
Multidirectional gaze-evoked nystagmus with mild cerebellar limb ataxia.
Ataxia Phenomenology Atlas (Part 3): Immune-Mediated, Paraneoplastic and Inflammatory Ataxias
Ataxia Phenomenology Atlas (Part 3): Immune-Mediated, Paraneoplastic and Inflammatory Ataxias
Alexander Disease
Video 13.46 (C13c46): Adult-Onset Alexander Disease
Palatal myoclonus, mild cerebellar ataxia, and the characteristic MRI “tadpole sign.”
CANVAS
Video 13.47 (C13c47): CANVAS (Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome)
Chronic cough, vestibular areflexia, sensory ataxia, and visual compensation during gait.
Post-Infectious and Autoimmune Ataxias
Video 13.49 (C13c49): Post-Infectious Cerebellitis with Myoclonus
Positive and negative myoclonus superimposed on mild cerebellar ataxia.
Video 13.50 (C13c50): Post-Infectious Opsoclonus-Myoclonus-Ataxia Syndrome (OMAS)
Opsoclonus, action myoclonus, and ataxia resolving with immunotherapy.
Video 13.51 (C13c51): Anti-GAD Cerebellar Ataxia
Progressive scanning dysarthria and severe gait instability.
Video 13.52 (C13c52): Advanced Anti-GAD Cerebellar Ataxia
Severe appendicular and gait ataxia with inability to stand independently.
Video 13.53 (C13c53): Para-Infectious OMAS
Florid opsoclonus, myoclonus, and ataxia with complete treatment response.
Video 13.54 (C13c54): Post-COVID OMAS
Ocular flutter, mild myoclonus, and cerebellar gait ataxia.
Video 13.55 (C13c55): Para-Infectious OMAS (Recovery Phase)
Resolving ocular flutter, action myoclonus, and gait instability.
Paraneoplastic Cerebellar Syndromes
Video 13.56 (C13c56): Anti-Yo Cerebellar Degeneration
Scanning dysarthria, tremor, dysmetria, and severe gait ataxia.
Video 13.57 (C13c57): Advanced Anti-Yo Cerebellar Degeneration
Head tremor, severe cerebellar dysarthria, and appendicular ataxia.
Video 13.58 (C13c58): Paraneoplastic Cerebellar Degeneration
Severe titubation, cerebellar tremor, and inability to ambulate independently.
Video 13.59 (C13c59): Cerebellar (Holmes-Type) Tremor in Paraneoplastic Disease
Severe unilateral proximal tremor with marked target impairment.
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