Parkinson Disease: Florida

Liu B. · Department of Pharmacodynamics, College of Pharmacy, the McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. · AAPS J. · Pubmed #17025278 links to  free full text

Abstract: Parkinson's disease (PD) is a debilitating movement disorder resulting from a progressive degeneration of the nigrostriatal dopaminergic pathway and depletion of neurotransmitter dopamine in the striatum. Molecular cloning studies have identified nearly a dozen genes or loci that are associated with small clusters of mostly early onset and genetic forms of PD. The etiology of the vast majority of PD cases remains unknown, and the precise molecular and biochemical processes governing the selective and progressive degeneration of the nigrostriatal dopaminergic pathway are poorly understood. Current drug therapies for PD are symptomatic and appear to bear little effect on the progressive neurodegenerative process. Studies of postmortem PD brains and various cellular and animal models of PD in the last 2 decades strongly suggest that the generation of pro-inflammatory and neurotoxic factors by the resident brain immune cells, microglia, plays a prominent role in mediating the progressive neurodegenerative process. This review discusses literature supporting the possibility of modulating the activity of microglia as a neuroprotective strategy for the treatment of PD.

Uitti RJ, Wszolek ZK. · Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA. · J Neural Transm Suppl. · Pubmed #17017564 No free full text.

Abstract: Studying potential neuroprotective therapy for Parkinson's disease is conceptually problematic because of the heterogenous nature of the Parkinson's syndrome and complexities in operational definitions for neuroprotection. The current literature concerning neuroprotection provides no convincing evidence of any treatment as definitively neuroprotective in Parkinson's disease. Recent clinical trials and novel trial designs are reviewed that may identify meaningful therapy, resulting in maintenance of neurological function and quality of life for persons with Parkinson's disease.

Whaley NR, Uitti RJ, Dickson DW, Farrer MJ, Wszolek ZK. · Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA. · J Neural Transm Suppl. · Pubmed #17017533 No free full text.

Abstract: The etiology for Parkinson's disease (PD) remains unknown. Genetic causes have been identified with several distinct mutations. Recently, 9 mutations involving a novel gene, leucine-rich repeat kinase 2 (LRRK2), have been identified as the cause of autosomal dominant PD in kindreds, with some of them previously linked to the PARK8 locus on chromosome 12. LRRK2 mutations are relatively common genetic causes of familial and sporadic PD. In addition, these mutations have been identified in diverse populations. The clinical and pathologic features of LRRK2-associated PD are indistinguishable from idiopathic PD; however, considerable clinical and pathologic variability exists even among kindreds. This short review highlights the clinical and pathologic features in LRRK2-associated parkinsonism.

Hauser RA. · Parkinson's Disease and Movement Disorders Center, National Parkinson Foundation Center of Excellence, University of South Florida, Tampa, FL, USA. · Geriatrics. · Pubmed #16989543 No free full text.

Abstract: Long-term care of elderly patients with Parkinson's disease (PD) is challenging for long-term care staff and physicians. Because the progression of PD varies among patients, an individualized treatment plan, updated as necessary based on disease progression, comorbid conditions, and side effects, is essential. Education regarding PD management is also needed to provide optimal care, and treatment guidelines from professional associations are available. Especially important is the management of motor complications, which usually emerge after treatment with antiparkinsonian medications, particularly levodopa/carbidopa. Current treatment strategies to avoid or treat motor complications aim at providing a more continuous (ie, physiologic) dopaminergic stimulation, rather than the pulsatile (intermittent) stimulation provided by traditional PD treatments. Catechol O-methyltransferase (COMT) inhibitors prolong the levodopa serum half-life and allow more levodopa to be delivered to the brain over a longer time, thereby smoothing dopaminergic stimulation. Dopamine agonists also provide more continuous dopaminergic stimulation but are associated with a greater likelihood of hallucinations and confusion, especially in the elderly. Treatments that reduce motor complications, allowing a higher level of functioning, lessen the burden of care in long-term care settings and increase quality of life for patients and their families.

Gilbert-Barness E, Barness LA. · Department of Pathology, University of South Florida College of Medicine, Tampa General Hospital, Tampa, Florida 33606, USA. · Am J Med Genet A. · Pubmed #16969859 No free full text.

Abstract: Fetal dysrhythmias are usually transient. Abnormal fetal rates and rhythms during labor are "functional." Fetal dysrhythmias may be associated with congenital heart disease and fetal hydrops. Bradycardia is usually related to fetal distress; supraventricular tachycardia, atrial flutter, and atrial fibrillation may be associated with severe congestive heart failure. Ventricular fibrillation is rare in the fetus and infant and is usually associated with myocardial necrosis with perimembranous septal defect; the nonbranching atrioventricular (AV) bundle may have an aberrant position and result in cardiac arrhythmia. Wolff-Parkinson-White syndrome with conduction abnormalities and left ventricular hypertrophy (LVH) is due to an accessory pathway that bypasses the AV sulcus and results in faster conduction. Carnitine deficiency may be primary or secondary and may result in cardiac arrhythmia. Histiocytoid cardiomyopathy is characterized by cardiomegaly, incessant ventricular tachycardia, and frequently sudden death. Arrhythmogenic right ventricular dysplasia (ARVD) results in ventricular tachycardia and left bundle branch block. Noncompaction of the left ventricle predisposes to potentially fatal arrhythmias. Long Q-T syndromes (LQTS) are a heterogeneous group of disorders with many genetic mutations. Brugada syndrome is an autosomal dominant trait with right bundle branch block and ST elevation. Barth syndrome is an X-linked disorder with dilated cardiomyopathy, cyclic neutropenia and skeletal myopathy. Hypertrophic cardiomyopathy in infancy may be related to metabolic diseases, particularly glycogen storage diseases; the familial form predisposes to sudden death. Arrhythmias following cardiac surgery may occur after closure of a ventricular septal defect (VSD) or damage to the conduction system.

Tribl F, Marcus K, Bringmann G, Meyer HE, Gerlach M, Riederer P. · The National Parkinson Foundation (NPF) Research Laboratories, Miami, FL, USA. · J Neural Transm. · Pubmed #16835691 No free full text.

Abstract: Proteomics is a promising approach, which provides information about the expression of proteins and increasingly finds application in life science and disease research. Meanwhile, proteomics has proven to be applicable even on post mortem human brain tissue and has opened a new area in neuroproteomics. Thereby, neuroproteomics is usually employed to generate large protein profiles of brain tissue, which mostly reflect the expression of highly abundant proteins. As a complementary approach, the focus on sub-proteomes would enhance more specific insight into brain function. Sub-proteomes are accessible via several strategies, including affinity pull-down approaches, immunoprecipitation or subcellular fractionation. The extraordinary potential of subcellular proteomics to reveal even minute differences in the protein constitution of related cellular organelles is exemplified by a recent global description of neuromelanin granules from the human brain, which could be identified as pigmented lysosome-related organelles.

Skidmore FM, Rodriguez RL, Fernandez HH, Goodman WK, Foote KD, Okun MS. · Department of Neurology, McKnight Brain Institute, University of Florida College of Medicine in Gainesville, 32610, USA. · CNS Spectr. · Pubmed #16816792 links to  free full text

Abstract: The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that "chronically" implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.

Zesiewicz TA, Wecker L, Sullivan KL, Merlin LR, Hauser RA. · Parkinson's Disease and Movement Disorders Center, University of South Florida, Tampa, 33612, USA. · Clin Neuropharmacol. · Pubmed #16772808 No free full text.

Abstract: Levodopa treatment of Parkinson disease results in hyperhomocysteinemia (HHcy) as a consequence of levodopa methylation by catechol-O-methyltransferase (COMT). Although inhibition of COMT should theoretically prevent or reduce levodopa-induced HHcy, results from several prospective studies are conflicting. Our review of these studies suggests that the ability of COMT inhibition to reduce or prevent levodopa-induced HHcy in Parkinson disease patients may be attributed to differences in the vitamin status of the study participants. In patients with low or low-normal folate levels, levodopa administration is associated with a greater increase in homocysteine and concomitant entacapone administration is associated with a greater reduction in homocysteine.

Papapetropoulos S. · Department of Neurology, University of Miami, Miller School of Medicine, Rm. 4004, 1501 NW 9th Ave., FL 33136, USA. · J Neuropsychiatry Clin Neurosci. · Pubmed #16720791 links to  free full text

Abstract: Visual hallucinations in Parkinson's disease are usually treatment-related and occur in at least 30% of patients. Although their clinical and epidemiological features have been extensively reviewed, their etiopathogenesis remains a matter of debate. Based on the current evidence available, this review suggests that regional neurodegeneration of the ventral dopaminergic pathway, as evident in the aggregation of the protein alpha-synuclein, is the main event linked to the development of visual hallucinations in Parkinson's disease. Denervation supersensitivity of dopaminergic receptors in ventral striatal and mesocorticolimbic areas as well as defective synaptic buffering ability due to the loss of dopaminergic presynaptic terminals and dopamine transporter may be among the key factors leading to visual hallucinations in Parkinson's disease.

Melrose HL, Lincoln SJ, Tyndall GM, Farrer MJ. · Department of Neuroscience, Genetics of Parkinsonism and Related Disorders, Morris K. Udall Parkinson' Disease Research Center of Excellence, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. · Exp Brain Res. · Pubmed #16639500 No free full text.

Abstract: Parkinson's disease (PD) is a multifactorial disease with a complex etiology that results from genetic risk factors, environmental exposures and most likely a combination of both. Rodent models of parkinsonism aim to reproduce key pathogenic features of the syndrome including movement disorder induced by the progressive loss of dopaminergic neurons in the substantia nigra, accompanied by the formation of alpha-synuclein containing Lewy body inclusions. Despite the creation of many excellent models, both chemically induced and genetically engineered, there is none that accurately demonstrates these features. Recent pathological staging studies in man have also emphasized the significant non-CNS component of PD that has yet to be tackled. Herein, we summarize rodent models of PD and what they offer to the field, and suggest future challenges and opportunities.

Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. · Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA. · Trends Neurosci. · Pubmed #16616379 No free full text.

Abstract: Parkinson's disease (PD) is the most common motor neurodegenerative disease. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have been linked recently with autosomal-dominant parkinsonism that is clinically indistinguishable from typical, idiopathic, late-onset PD. Thus, the protein LRRK2 has emerged as a promising therapeutic target for treatment of PD. LRRK2 is extraordinarily large and complex, with multiple enzymatic and protein-interaction domains, each of which is targeted by pathogenic mutations in familial PD. This review places the PD-associated mutations of LRRK2 in a structural and functional framework, with the ultimate aim of deciphering the molecular basis of LRRK2-associated pathogenesis. This, in turn, should advance our understanding and treatment of familial and idiopathic PD.

Farrer MJ. · Morris K. Udall Parkinsons Disease Research Center of Excellence, Birdsall Building, Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, Florida 32224, USA. · Nat Rev Genet. · Pubmed #16543934 No free full text.

Abstract: Parkinson disease is a complex, multifactorial neurodegenerative disease. Although a heritable basis was originally thought unlikely, recent studies have implicated several genes in its pathogenesis, and molecular findings now allow accurate diagnosis and challenge past criteria for defining Parkinson disease. Most importantly, genetic insights provide the rationale for new strategies for prevention or therapy, and have led to animal models of disease in which these strategies can be tested. Neuroprotective therapies can now be designed to slow or halt disease progression in affected subjects and asymptomatic carriers.

Taylor JP, Mata IF, Farrer MJ. · Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA. · Trends Mol Med. · Pubmed #16406842 No free full text.

Abstract: The presence of alpha-synuclein Lewy body pathology is used to distinguish Parkinson's disease from parkinsonism, for which a broader spectrum of neuropathologies, including tau-immunopositive neurofibrillary tangles and ubiquitin inclusions, might accompany nigral neuronal loss. These neuropathologies define the endpoint of many neurodegenerative disorders but might be symptomatic rather than causative. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) were recently discovered in late-onset parkinsonism, the phenotype of which can be clinically and pathologically indistinguishable from Parkinson's disease. However, in some kindreds with LRRK2- associated disease, pathologically distinct forms of parkinsonism, including nigral neuronal loss with Lewy body disease or tau-immunopositive neurofibrillary tangles, were discovered. Understanding the molecular function of the LRRK2 protein and its associated pathways might elucidate the switch between Lewy body pathology and neurofibrillary tangles, and holds promise for prospective therapeutics that might slow or halt progression of many forms of parkinsonism.

Levin BE, Katzen HL. · Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA. · Adv Neurol. · Pubmed #16383214 No free full text.

Abstract: Early cognitive changes in patients with PD are often subtle and influenced by factors that interact with the disease process, including age of disease onset, medication, and the specific constellation of motor symptoms. These factors notwithstanding, ample evidence exists that specific cognitive changes occur early in the course of PD. This evidence does not imply that cognitive deficits are pervasive during the early stages. To the contrary, they are usually subtle and often difficult to detect without formal neuropsychological testing. Executive-function deficits are the most frequently reported cognitive problems and, given that executive skills are an integral part of many tasks, it follows that subtle difficulties may be seen on a wide range of cognitive measures, particularly in working memory and visuospatial dysfunction, two areas that rely heavily on executive skills. Whereas apraxia and language processing deficits occur infrequently, subtle changes in olfaction and contrast sensitivity have also been repeatedly observed. Finally, depressive symptoms are also common in the early stages of the disease. The significance of the early behavioral changes and their prognostic implications are largely unknown. Prospective studies are needed to understand the longitudinal course of early cognitive changes to determine whether they remain as circumscribed impairments or represent a precursor to a more widespread dementia.

Lieberman A. · Lieberman Parkinson Clinic, North Bay Village, FL 33141, USA. · Acta Neurol Scand. · Pubmed #16367891 No free full text.

Abstract: Major depression is present, at any given time, in 20-40% of Parkinson's disease (PD) patients, several times the prevalence in the general population. In addition, depression may precede the diagnosis of PD. These observations and reports of depression during deep brain stimulation of regions contiguous to the substantia nigra, as well as reports of dopamine agonist improving depression, suggest depression, rather than being mainly a psychological reaction to a debilitating disease, is part of PD. It is postulated that mesolimbic and mesocortical dopaminergic pathways that mediate affect, behavior, and cognition, contribute to depression in PD.

Manfredsson FP, Lewin AS, Mandel RJ. · Department of Neuroscience, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610-0024, USA. · Gene Ther. · Pubmed #16267570 No free full text.

Abstract: Parkinson's disease is a prevalent progressive degenerative disorder of the elderly. There is a current need for novel therapeutic strategies because the standard levodopa pharmacotherapy is only temporarily efficacious. Recently, there have been some high-profile successful preclinical results obtained in animal models of neurological disorders using small interfering RNAs delivered by viral vectors. RNA interference can theoretically be applied to Parkinson's disease since over-expression of various proteins is known to kill the dopamine neurons of the substantia nigra in animal models and in familial forms of Parkinson's disease. Potential RNA interfering strategies and caveats are discussed in this review.

Ross OA, Farrer MJ. · Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. · Biochem Soc Trans. · Pubmed #16042550 No free full text.

Abstract: PD (Parkinson's disease) is an aetiologically heterogeneous disorder characterized by a clinical phenotype consisting of resting tremor, rigidity and bradykinesia. Motor symptoms are associated with a progressive loss of dopaminergic neurons, with Lewy body inclusions within surviving neurons. Although heritability studies have shown evidence of familial aggregation, twin studies have provided limited support for a genetic aetiology. Nevertheless, classical linkage methods have nominated 11 regions of the genome and pathogenic mutations have been identified in several genes, including alpha-synuclein, parkin, ubiquitin C-terminal hydrolase L1, oncogene DJ-1, PTEN-induced protein kinase 1 and microtubule-associated protein tau. Most recently, heterozygous mutations in LRRK2 (leucine-rich repeat kinase 2) were found to cause late-onset, autosomal-dominant PD. Despite their consistent clinical phenotype, family members with LRRK2 mutations can have variable alpha-synuclein and tau pathologies. Lrrk2 is a member of the Roc (Ras of complex proteins) family, with Ras GTPase and MAPKKK (mitogen-activated protein kinase kinase kinase) catalytic domains. Thus its discovery highlights vesicle dynamics and secondary-messenger signalling in disease pathophysiology. To diagnose a disease accurately and effectively treat it, requires an understanding of its molecular pathogenesis. Herein, we provide an overview of the genetics of PD, how these discoveries are revolutionizing long-held beliefs and more importantly how this knowledge may be translated into patient therapy.

Papapetropoulos S, Mash DC. · Department of Neurology, University of Miami, School of Medicine, Room 4004, 1501 NW 9th Avenue, Miami FL 33136, USA. · J Neurol. · Pubmed #15999234 No free full text.

Abstract: Psychotic symptoms are common in Parkinson's disease (PD) and occur in at least 20% of medication-treated patients. Benign visual hallucinations usually appear earlier, while malignant hallucinations, confusional states, delusions, paranoid beliefs, agitation, and delirium become more frequent with disease progression. Virtually all antiparkinsonian drugs may produce psychotic symptoms. Cognitive impairment, increased age, disease duration and severity, depression, and sleep disorders have been consistently identified as independent risk factors for their development. Although the precise pathoetiologic mechanisms remain unknown, we review evidence that links ventral dopaminergic pathway dysfunction (overactivity) together with the involvement of other neurotransmitter system imbalances as likely contributors. The clinical importance of the proposed mechanism is that successful management of psychotic symptoms in PD may rely on a multitarget approach to restore neurotransmitter imbalances rather than focusing exclusively on the dopaminergic dysfunction.

Hauser RA, Schwarzschild MA. · Department of Neurology, University of South Florida and Tampa General Healthcare, Tampa, Florida 33606, USA. · Drugs Aging. · Pubmed #15974638 No free full text.

Abstract: Long-term disability in Parkinson's disease (PD) is related to progression of the underlying disease and the emergence of complications of chronic levodopa therapy. There is a need for new medications that can slow the underlying progression of degeneration, improve PD symptoms in early disease without inducing dyskinesia, and improve motor fluctuations and 'off' time in advanced disease without worsening dyskinesia. Much interest has focused on the development of nondopaminergic therapies, with antagonists of the adenosine A2A receptor emerging as leading candidates. A2A receptors are selectively expressed in the basal ganglia and specific A2A antagonists reverse motor deficits without causing dyskinesia in animal models of PD. The antiparkinsonian potential of A2A receptor blockade has been expanded further by convergent epidemiological and laboratory findings suggesting a possible neuroprotective effect of A2A receptor antagonists in PD. Istradefylline (KW-6002) is the first of several adenosine A2A receptor antagonists in development for PD to advance to phase III clinical trials. Initial studies indicate that in patients with motor fluctuations on levodopa, addition of istradefylline reduces 'off' time. Additional studies are necessary to evaluate the benefit of istradefylline as monotherapy in early disease, its effect on the development of dyskinesia, and its effect on disease progression.

Eriksen JL, Wszolek Z, Petrucelli L. · Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. · Arch Neurol. · Pubmed #15767499 links to  free full text

Abstract: Parkinson disease (PD), the most common neurodegenerative movement disorder, is characterized by an extensive and progressive loss of dopaminergic neurons in the substantia nigra pars compacta. One of the pathological hallmarks of PD is the presence of Lewy bodies, intracellular inclusions of aggregated alpha-synuclein. Although the cause and pathogenesis of selective loss of dopamine neurons and the accumulation of alpha-synuclein in PD remain elusive, growing lines of evidence from environmental risk factors and early-onset genetics point to a convergence between energy metabolism and the disposal of damaged proteins in the development of PD. These findings suggest that impairments in mitochondrial and ubiquitin-proteasome system function can significantly contribute to the pathogenesis of PD. This review will summarize recent insights gained from genetic and environmental studies of PD that underscore this association.

Eriksen JL, Przedborski S, Petrucelli L. · Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA. · Trends Mol Med. · Pubmed #15760766 No free full text.

Abstract: Four recent papers related specifically to the familial form of Parkinson's disease reinforce the idea that endogenous levels of alpha-synuclein can strongly influence disease phenotype. Two recent publications of alpha-synuclein-duplication mutations show that the severity of familial Parkinsonian phenotype is dependent upon SNCA gene dosage and corresponding protein levels. Familial point mutations in SNCA were found to impair the efficient lysosomal degradation of alpha-synuclein, potentially resulting in elevated levels of alpha-synuclein. Conversely, the complete knockout of SNCA has little effect on transgenic mice. It is now clear that the regulation of alpha-synuclein levels has potential significance in the pathogenesis and treatment of sporadic PD.

Bruce BB, Foote KD, Rosenbek J, Sapienza C, Romrell J, Crucian G, Okun MS. · Department of Neurology, McKnight Brain Institute, Movement Disorders Center, University of Florida, Gainesville, FL 32610, USA. · Stereotact Funct Neurosurg. · Pubmed #15557767 No free full text.

Abstract: Patients may present with classical symptoms suggesting aphasia following thalamotomy (repetition, comprehension, fluency and naming abnormalities). They may also present with 'freezing of speech', and this symptom should not be considered as a speech disorder or a symptom of Parkinson's disease progression, without careful testing to rule out language deficits, particularly dysfluency. There are important issues related to all language complications of thalamotomy, including (1) the time course of problems following surgery, (2) the impact of preexistingspeech problems, (3) the importance of the size and location of lesions, (4) the potential circuits important in the pathogenesis of a thalamic language disturbance and (5) whether laterality makes a difference (left- versus right-sided thalamic lesions). As more centers switch from thalamotomy to deep brain stimulation, the issues regarding aphasia will need to be addressed.

Hauser RA, Lyons KE. · Department of Neurology, University of South Florida and Tampa General Healthcare, Tampa, FL 33606, USA. · Neurol Clin. · Pubmed #15501363 No free full text.

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Wint DP, Okun MS, Fernandez HH. · Department of Psychiatry, McKnight Brain Institute/University of Florida, Gainesville 32610, USA. · J Geriatr Psychiatry Neurol. · Pubmed #15312276 No free full text.

Abstract: Psychosis in Parkinson's disease (PD) is a fairly common and vexing problem. Although it can occur at any stage of the illness, it is a particularly important issue for patients who are in the later stages of PD and have been chronically treated with anti-PD medications. The exact pathophysiology of PD-related psychosis remains a mystery. Neurochemical imbalances, sleep disturbances, and visual processing abnormalities in PD have been implicated in its pathogenesis. Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient's anti-PD medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic agent is presently the treatment of choice. An emerging treatment option is the use of acetylcholinesterase inhibitors. This article reviews what is known about the epidemiology, risk factors, pathophysiology, and treatment of PD-related psychosis.

Petrucelli L, Dawson TM. · Mayo Clinic, Jacksonville, USA. · Ann Med. · Pubmed #15224658 No free full text.

Abstract: Many neurodegenerative disorders such as Alzheimer's disease (AD) Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD) are characterized by neuronal damage that may be caused by toxic, abnormal, aggregation-prone proteins. The purpose of this review is threefold: 1) to provide the reader with an overview of the genes involved in the abnormal processing and accumulation of misfolded proteins in neurodegenerative diseases using PD as a model disease; 2) to understand the cellular mechanisms for disposal of abnormal proteins, and the effects of toxic protein accumulation on ubiquitin proteasome system (UPS) and neuronal survival and 3) to discuss the development and challenges of cell culture and animal models for a rational and effective treatment for these disorders.