Infectious agents and Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of dementia worldwide. Individuals affected by the disease gradually lose their capacity for abstract thinking, understanding, communication and memory. As populations age, declining cognitive abilities will represent an increasing global health concern. While AD was first described over a century ago, its pathogenesis remains to be fully elucidated. It is believed that cognitive decline in AD is caused by a progressive loss of neurons and synapses that lead to reduced neural plasticity. AD is a multifactorial disease affected by genetic and environmental factors. The molecular hallmarks of AD include formation of extracellular ß amyloid (Aß) aggregates, neurofibrillary tangles of hyperphosphorylated tau protein, excessive oxidative damage, an imbalance of biothiols, dysregulated methylation, and a disproportionate inflammatory response. Recent reports have shown that viruses (e.g., Herpes simplex type 1, 2, 6A/B; human cytomegalovirus, Epstein-Barr virus, hepatitis C virus, influenza virus, and severe acute respiratory syndrome coronavirus 2, SARS-CoV-2), bacteria (e.g., Treponema pallidum, Borrelia burgdorferi, Chlamydia pneumoniae, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcmitans, Eikenella corrodens, Treponema denticola, and Helicobacter pylori), as well as eukaryotic unicellular parasites (e.g., Toxoplasma gondii) may factor into cognitive decline within the context of AD. Microorganisms may trigger pathological changes in the brain that resemble and/or induce accumulation of Aß peptides and promote tau hyperphosphorylation. Further, the mere presence of infectious agents is suspected to induce both local and systemic inflammatory responses promoting cellular damage and neuronal loss. Here we review the influence of infectious agents on the development of AD to inspire new research in dementia based on these pathogens.

Molecular Factors Mediating Neural Cell Plasticity Changes in Dementia Brain Diseases.

Neural plasticity-the ability to alter a neuronal response to environmental stimuli-is an important factor in learning and memory. Short-term synaptic plasticity and long-term synaptic plasticity, including long-term potentiation and long-term depression, are the most-characterized models of learning and memory at the molecular and cellular level. These processes are often disrupted by neurodegeneration-induced dementias. Alzheimer's disease (AD) accounts for 50% of cases of dementia. Vascular dementia (VaD), Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD) constitute much of the remaining cases. While vascular lesions are the principal cause of VaD, neurodegenerative processes have been established as etiological agents of many dementia diseases. Chief among such processes is the deposition of pathological protein aggregates in vivo including ß-amyloid deposition in AD, the formation of neurofibrillary tangles in AD and FTD, and the accumulation of Lewy bodies composed of α-synuclein aggregates in DLB and PDD. The main symptoms of dementia are cognitive decline and memory and learning impairment. Nonetheless, accurate diagnoses of neurodegenerative diseases can be difficult due to overlapping clinical symptoms and the diverse locations of cortical lesions. Still, new neuroimaging and molecular biomarkers have improved clinicians' diagnostic capabilities in the context of dementia and may lead to the development of more effective treatments. Both genetic and environmental factors may lead to the aggregation of pathological proteins and altered levels of cytokines, such that can trigger the formation of proinflammatory immunological phenotypes. This cascade of pathological changes provides fertile ground for the development of neural plasticity disorders and dementias. Available pharmacotherapy and disease-modifying therapies currently in clinical trials may modulate synaptic plasticity to mitigate the effects neuropathological changes have on cognitive function, memory, and learning. In this article, we review the neural plasticity changes seen in common neurodegenerative diseases from pathophysiological and clinical points of view and highlight potential molecular targets of disease-modifying therapies.

Migraine: Calcium Channels and Glia.

Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and migraine without aura. According to the neurovascular theory of migraine, the activation of the trigeminovascular system (TGVS) and the release of numerous neuropeptides, including calcitonin gene-related peptide (CGRP) are involved in headache pathogenesis. TGVS can be activated by cortical spreading depression (CSD), a phenomenon responsible for the aura. The mechanism of CSD, stemming in part from aberrant interactions between neurons and glia have been studied in models of familial hemiplegic migraine (FHM), a rare monogenic form of migraine with aura. The present review focuses on those interactions, especially as seen in FHM type 1, a variant of the disease caused by a mutation in CACNA1A, which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel.

Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine.

BACKGROUND: Migraine is a polygenetic disease, considered as a channelopathy. The dysregulation of ion functioning due to genetic changes may activate the trigeminovascular system and induce migraine attack both migraine with aura (MA) and without aura (MO). OBJECTIVES: The aim of the study was to analyze the following variants of genes encoding ion channels and associated protein: c.3199G>A SCN1A, c.56G>A SCN2A, c.28A>G and c.328T>C KCNK18, c.3053A>G TRPA1, c.31-1811C>T STX1A in migraine patients. PATIENTS AND METHODS: The study included 170 migraine patients and 173 controls. HRMA and Sanger sequencing were used for genotyping. Meta-analysis was performed for c.28A>G, c.328T>C KCNK18, and c.31-1811C>T STX1A. RESULTS: AA genotype of c.56G>A SCN2A was found only in migraine patients. Patients with c.328T>C KCNK18 mutation had an increased risk of developing migraine before the age of 18. Moreover, individuals with AA/TC haplotype of KCNK18 had higher attack frequency than those with AA/TT (p<0.05). T allele of c.31-1811C>T STX1A was more frequent in MA patients than MO (p<0.05). The c.3053A>G TRPA1 polymorphism was more common in patients with migraine onset before the age of 15 (p<0.05), while c.31-1811C>T STX1A and c.3199G>A SCN1A before the age of 10 (p<0.01). Meta-analysis showed a significant association of c.31-1811C>T STX1A polymorphism with migraine overall (OR=1.22, p=0.0086), MA, and MO. No association was found for c.28A>G KCNK18, c.328T>C KCNK18, and migraine overall. CONCLUSION: Changes in genes encoding ion channels or proteins regulating their functioning may increase the risk of migraines and correlate with clinical features of disease, e.g. age of onset and attack frequency.

Genetic factors related to the immune system in subjects at risk of developing Alzheimer's disease.

Alzheimer's disease is the most common neurodegenerative disease and the cause of dementia. Although the pathomechanisms underlying Alzheimer's disease have not been fully elucidated, there is evidence that genetic and environmental factors contribute to its development. Immune system changes, both environmentally-induced and, as a result of predisposing genetics, are implicated in Alzheimer's disease etiopathogenesis. Genes associated with immune system dysfunction in Alzheimer's disease include CLU, BIN1, CR1, ABCA7, HLA-DRB1, TREM2, EPHA1, and CD2AP. In particular, BIN1 and CLU, aberrations in which are thought to promote neurodegeneration by dysregulating exocytosis and immune processes, together with the E4 variant of the APOE gene, are among the most common genetic risk factors for Alzheimer's disease. While the relationships between these genes in Alzheimer's disease have been examined, little information exists regarding their role as variables predisposing first or second-degree relatives of Alzheimer's disease patients to the illness. The rationale of this review is to suggest that individuals with a family history of Alzheimer's disease who have the BIN1-T/T variant may be at significant risk of developing Alzheimer's disease. Also, the unfavorable BIN1-T variant is independent of APOE E4-associated risk. People at risk of developing Alzheimer's disease are more often carriers of the protective C-variant of the CLU gene, the presence of which might be associated with later-onset dementia observable within this high-risk group. It seems BIN1 and CLU together with, albeit independent of APOE E4, may be among the factors predisposing individuals with a family history of Alzheimer's disease to developing the illness.

Assessment of serum selenium concentration in patients with autoimmune thyroiditis in Poznan district.

Autoimmune thyroiditis (AIT) is characterised by infiltration of lymphocytes and destruction of thyroid gland. It results from the interaction of genetic predisposition and environmental triggers. Among environmental factors some infections, medications and inadequate micronutrients supply like selenium (Se) deficiency are believed to play a role. AIM: The aim of our study was to assess the serum selenium concentration in patients with AIT and healthy volunteers in the Polish population living in the Poznan district, and to compare our results with similar trials conducted on other European AIT groups. MATERIALS AND METHODS: Fifty three patients with AIT were included in the study. Elevated thyroperoxidase antibodies and/or thyroglobulin antibodies concentration and abnormalities typical for AIT in the thyroid ultrasound were the inclusion criteria. A control group consisted of 36 healthy, age and sex-matched volunteers. RESULTS: The median Se concentration was 56.67 µg/L in the AIT group and 39.75 µg/L in the controls (p>0.05). Decreased Se concentration was observed in 62% of the patients and in 72% of the controls (p=0.47). There was no statistically significant difference in Se status in AIT group when compared to the other Polish, German, Austrian, Dutch and Greek populations with AIT. Significantly higher values were observed in Italian and Greek study when compared to present results in AIT group. CONCLUSIONS: No association between selenium status and prevalence of autoimmune thyroiditis in Polish population living in Poznan district was noticed. Nevertheless determination of the normal serum Se concentration for European populations is necessary. Further studies with enlarged studied groups should be implemented.

Analysis of PRKN Variants and Clinical Features in Polish Patients with Parkinson's Disease.

The etiology of Parkinson's disease (PD) is still unclear, but mutations in PRKN have provided some biological insights. The role of PRKN mutations and other genetic variation in determining the clinical features of PD remains unresolved. The aim of the study was to analyze PRKN mutations in PD and controls in the Polish population and to try to correlate between the presence of genetic variants and clinical features. We screened for PRKN mutations in 90 PD patients and 113 controls and evaluated clinical features in these patients. We showed that in the Polish population 4% of PD patients had PRKN mutations (single or with additional polymorphism) while single heterozygous polymorphisms (S167N, E310D, D394N) of PRKN were present in 21% of sporadic PD. Moreover, 5% PD patients had more than one PRKN change (polymorphisms and mutations). Detected PRKN variants moderately correlated with PD course and response to L-dopa. It also showed that other PARK genes (SNCA, HTRA2, SPR) mutations probably may additionally influence PD risk and clinical features. PRKN variants are relatively common in our Polish series of patients with PD. Analysis of the PRKN gene may be useful in determining clinical phenotype, and helping with diagnostic and prognostic procedures in the future.

Serum homocysteine levels are decreased in levothyroxine-treated women with autoimmune thyroiditis.

BACKGROUND: Hyperhomocysteinemia is a well-known cardiovascular risk factor and its elevation is established in overt hypothyroidism. Since some authors suggest that chronic autoimmune thyroiditis per se may be considered as a novel risk factor of atherosclerosis independent of thyroid function, the analysis of classical cardiovascular risk factors might be helpful in evaluation the causative relationship. Data concerning the impact of thyroid autoimmunity in euthyroid state on homocysteine (Hcy) level is lacking. The aim of this study was to evaluate Hcy level in context of anti-thyroperoxidase antibodies (TPOAbs) in euthyroidism. METHODS: It is a case-control study. 31 euthyroid women treated with levothyroxine (L-T4) due to Hashimoto thyroiditis (HT) and 26 females in euthyroidism without L-T4 replacement therapy were enrolled in the study. All women with HT had positive TPOAbs. Forty healthy females negative for TPOAbs comparable for age and body mass index (BMI) participated in the study as controls. Exclusion criteria were a history of any acute or chronic disease, use of any medications (including oral contraceptives and vitamin supplements), smoking, alcoholism. RESULTS: TPOAbs titers were higher in both groups of HT patients versus the healthy controls. Hcy levels were found to be significantly lower in treated HT patients (Me 11 µmol; IQR 4.2 µmol) as compared with healthy controls (Me 13.35 µmol; IQR 6.34 µmol; p = 0.0179). In contrast, no significant difference was found between non treated HT and control group in Hcy level. The study groups and the controls did not differ in age and BMI. Furthermore, levels of TSH, FT4, TC, LDL, HDL and TAG did not differ between the study group and the control group. CONCLUSION: The main finding of the study is a decrease in Hcy level in treated HT as compared with healthy controls. Based on our observations one can also assume that correct L-T4 replacement was associated here with a decrease of Hcy. Furthermore, it seems that non treated HT in euthyroidism is not associated with Hcy increase, in contrast to overt hypothyroidism. This may be just another argument against the concepts about the role of "euthyroid HT" in the development of atherosclerosis.

Molecular Effects of L-dopa Therapy in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurological diseases in elderly people. The mean age of onset is 55 years of age, and the risk for developing PD increases 5-fold by the age of 70. In PD, there is impairment in both motor and nonmotor (NMS) functions. The strategy of PD motor dysfunction treatment is simple and generally based on the enhancement of dopaminergic transmission by means of the L-dihydroxyphenylalanine (L-dopa) and dopamine (DA) agonists. L-dopa was discovered in the early -60's of the last century by Hornykiewicz and used for the treatment of patients with PD. L-dopa treatment in PD is related to decreased levels of the neurotransmitter (DA) in striatum and ab-sence of DA transporters on the nerve terminals in the brain. L-dopa may also indirectly stimulate the receptors of the D1 and D2 families. Administration of L-dopa to PD patients, especially long-time therapy, may cause side effects in the form of increased toxicity and inflammatory response, as well as disturbances in biothiols metabolism. Therefore, in PD pa-tients treated with L-dopa, monitoring of oxidative stress markers (8-oxo-2'-deoxyguanosine, apoptotic proteins) and in-flammatory factors (high-sensitivity C-reactive protein, soluble intracellular adhesion molecule), as well as biothiol com-pounds (homocysteine, cysteine, glutathione) is recommended. Administration of vitamins B6, B12, and folates along with an effective therapy with antioxidants and/or anti-inflammatory drugs at an early stage of PD might contribute to improvement in the quality of the life of patients with PD and to slowing down or stopping the progression of the disease.

Genetic variants in diseases of the extrapyramidal system.

Knowledge on the genetics of movement disorders has advanced significantly in recent years. It is now recognized that disorders of the basal ganglia have genetic basis and it is suggested that molecular genetic data will provide clues to the pathophysiology of normal and abnormal motor control. Progress in molecular genetic studies, leading to the detection of genetic mutations and loci, has contributed to the understanding of mechanisms of neurodegeneration and has helped clarify the pathogenesis of some neurodegenerative diseases. Molecular studies have also found application in the diagnosis of neurodegenerative diseases, increasing the range of genetic counseling and enabling a more accurate diagno-sis. It seems that understanding pathogenic processes and the significant role of genetics has led to many experiments that may in the future will result in more effective treatment of such diseases as Parkinson's or Huntington's. Currently used molecular diagnostics based on DNA analysis can identify 9 neurodegenerative diseases, including spinal cerebellar ataxia inherited in an autosomal dominant manner, dentate-rubro-pallido-luysian atrophy, Friedreich's disease, ataxia with ocu-lomotorapraxia, Huntington's disease, dystonia type 1, Wilson's disease, and some cases of Parkinson's disease.

[Homocysteine and cognitive functions in bipolar depression]. / Homocysteina a funkcje poznawcze w depresji w przebiegu choroby afektywnej dwubiegunowej.

AIM: The aim of the study was to evaluate a relationship between concentrations of hoocysteine (HCY), vitamin B12 and folic acid and disturbances of cognitive functions during acute episode of bipolar depression. METHODS: 116 patients were studied (93 women, 23 men), aged 20-78 (mean 51±13) years during acute episode of bipolar depression. Depression was evaluated by the 17-item Hamilton's Depression Rating Scale (HDRS). The following tests measuring cognitive functions were applied: Trail Making Test, Wisconsin Card Sorting Test, Stroop Test and Wechsler Adult Intelligence Scale-Revised. In all patients, the measurements of serum homocysteine, vitamin B12 and folic acid were carried out. RESULTS: Hyperhomocystemia (HCY>15µM/l) was detected in 41 patients (35%), more frequently in men (52%) than in women (31%). Patients with hyperhomocysteinemia achieved worse results in sub-tests of WAIS-R (verbal understanding and perceptional organization). In men, negative correlation was found between HCY concentration and number of errors in Stroop Test, and WCST (total errors and non-perseverative errors). In women with bipolar disorder, type II, negative correlation between HCY concentration and time of Stroop Test, and between vitamin B12 concentration and number of errors in Stroop Test, were demonstrated. In the whole group and in men, there was positive correlation between higher folic acid concentration and the number of errors in Stroop Test. CONCLUSIONS: The results obtained show higher HCY concentration in considerable proportion of patients with bipolar depression, especially in men. They also confirm a connect between high homocysteine concentration and worse performance in some neuropsychological tests. Such relationship was more marked in men.

[Alpha-synuclein in Parkinson's disease]. / Alfa-synukleina w chorobie Parkinsona.

Parkinson's disease (PD) is a degenerative disease of the central nervous system, of which patomechanizm entirely is not clear. In the picture neuropathologically there is observed degeneration and loss of dopaminergic neurons, but also noradrenergic, serotonergic and cholinergic neurons in patients with PD. It is believed, that causes of PD are both environmental and genetic factors, associated mainly with mutations in the SNCA and PRKN genes, which may lead to changes in the structure of proteins such as alpha-synuclein (ASN) and Parkin. In neurons, disorders of the protein structure can lead to its aggregation and formation of soluble oligomers and insoluble filaments in the form of Lewy bodies and Lewy neuritis. In PD aggregation of ASN can be modulated by many factors like: oxidative stress, other neuronal proteins, Parkin, catecholamines especially dopamine, and mutations of SNCA gene. It also appears that some impact on the aggregation of ASN may have destabilizing factors of ASN tetramers. That, does ASN may become a new point for pharmacotherapy in PD.

Alzheimer's Disease and Vascular Dementia, Connecting and Differentiating Features.

Alzheimer's disease (AD) and vascular dementia (VD) are the leading causes of dementia, presenting a significant challenge in differential diagnosis. While their clinical presentations can overlap, their underlying pathologies are distinct. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles, leading to progressive neurodegeneration. VD, on the other hand, arises from cerebrovascular insults that disrupt blood flow to the brain, causing neuronal injury and cognitive decline. Despite distinct etiologies, AD and VD share common risk factors such as hypertension, diabetes, and hyperlipidemia. Recent research suggests a potential role for oral microbiota in both diseases, warranting further investigation. The diagnostic dilemma lies in the significant overlap of symptoms including memory loss, executive dysfunction, and personality changes. The absence of definitive biomarkers and limitations of current neuroimaging techniques necessitate a multi-modal approach integrating clinical history, cognitive assessment, and neuroimaging findings. Promising avenues for improved diagnosis include the exploration of novel biomarkers like inflammatory markers, MMPs, and circulating microRNAs. Additionally, advanced neuroimaging techniques hold promise in differentiating AD and VD by revealing characteristic cerebrovascular disease patterns and brain atrophy specific to each condition. By elucidating the complexities underlying AD and VD, we can refine diagnostic accuracy and optimize treatment strategies for this ever-growing patient population. Future research efforts should focus on identifying disease-specific biomarkers and developing more effective neuroimaging methods to achieve a definitive diagnosis and guide the development of targeted therapies.

Epigenetics and the neurodegenerative process.

Neurological diseases are multifactorial, genetic and environmental. Environmental factors such as diet, physical activity and emotional state are epigenetic factors. Environmental markers are responsible for epigenetic modifications. The effect of epigenetic changes is increased inflammation of the nervous system and neuronal damage. In recent years, it has been shown that epigenetic changes may cause an increased risk of neurological disorders but, currently, the relationship between epigenetic modifications and neurodegeneration remains unclear. This review summarizes current knowledge about neurological disorders caused by epigenetic changes in diseases such as Alzheimer's disease, Parkinson's disease, stroke and epilepsy. Advances in epigenetic techniques may be key to understanding the epigenetics of central changes in neurological diseases.

A Review of the CACNA Gene Family: Its Role in Neurological Disorders.

Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, including CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, and CACNA1H, in the pathogenesis of conditions such as migraine, epilepsy, cerebellar ataxia, dystonia, and cerebellar atrophy. Specifically, variants in CACNA1A have been linked to familial hemiplegic migraine and epileptic seizures, underscoring its importance in neurological disease etiology. Furthermore, different genetic variants of CACNA1B have been associated with migraine susceptibility, further highlighting the role of CACNA genes in migraine pathology. The complex relationship between CACNA gene variants and neurological phenotypes, including focal seizures and ataxia, presents a variety of clinical manifestations of impaired calcium channel function. The aim of this article was to explore the role of CACNA genes in various neurological disorders, elucidating their significance in conditions such as migraine, epilepsy, and cerebellar ataxias. Further exploration of CACNA gene variants and their interactions with molecular factors, such as microRNAs, holds promise for advancing our understanding of genetic neurological disorders.

Correction: Szymanowicz et al. Headache and NOTCH3 Gene Variants in Patients with CADASIL. Neurol. Int. 2023, 15, 1238-1252.

Figure Description [...].

Hyperhomocysteinemia in bipolar depression: clinical and biochemical correlates.

BACKGROUND: Depression may be associated with elevated homocysteine (HCY) levels. Procedures aiming at its decrease, i.e. supplementation with folic acid or vitamin B12, have antidepressant effect. Both depression and elevated HCY can increase cardiovascular risk. In this study, clinical and biochemical factors, including markers of endothelial function, in relation to hyperhomocysteinemia, in patients with bipolar depression during acute episode were studied. METHOD: One hundred and twelve patients (24 male, 88 female), aged 20-78 (mean 51 ± 14 years), with depressive episode in the course of bipolar mood disorder have been included. The assays were made of serum concentrations of HCY, vitamin B12, folic acid as well as markers of endothelial function such as E-selectin and intracellular adhesion molecule-1 (ICAM-1). RESULTS: Hyperhomocysteinemia (>15 mM) was found in 50 patients (45%), significantly more frequently in male (67%) than in female subjects (39%). Female patients with hyperhomocysteinemia were significantly older than the remaining ones. A significant inverse correlation between HCY level and concentration of folic acid and vitamin B12 as well as with E-selectin and ICAM-1 was observed. CONCLUSION: The results point to a significant prevalence of hyperhomocysteinemia in bipolar depressed patients during an acute episode. They also corroborate the correlation between increased concentration of HCY and lower level of vitamin B12 and folic acid. An unexpected finding of negative correlation of HCY level with markers of endothelial functions in such patients is discussed in view of current concepts of the role of HCY in various conditions.

Mutations in PRKN and SNCA Genes Important for the Progress of Parkinson's Disease.

Although Parkinson's disease (PD) was first described almost 200 years ago, it remains an incurable disease with a cause that is not fully understood. Nowadays it is known that disturbances in the structure of pathological proteins in PD can be caused by more than environmental and genetic factors. Despite numerous debates and controversies in the literature about the role of mutations in the SNCA and PRKN genes in the pathogenesis of PD, it is evident that these genes play a key role in maintaining dopamine (DA) neuronal homeostasis and that the dysfunction of this homeostasis is relevant to both familial (FPD) and sporadic (SPD) PD with different onset. In recent years, the importance of alphasynuclein (ASN) in the process of neurodegeneration and neuroprotective function of the Parkin is becoming better understood. Moreover, there have been an increasing number of recent reports indicating the importance of the interaction between these proteins and their encoding genes. Among others interactions, it is suggested that even heterozygous substitution in the PRKN gene in the presence of the variants +2/+2 or +2/+3 of NACP-Rep1 in the SNCA promoter, may increase the risk of PD manifestation, which is probably due to ineffective elimination of over-expressed ASN by the mutated Parkin protein. Finally, it seems that genetic testing may be an important part of diagnostics in patients with PD and may improve the prognostic process in the course of PD. However, only full knowledge of the mechanism of the interaction between the genes associated with the pathogenesis of PD is likely to help explain the currently unknown pathways of selective damage to dopaminergic neurons in the course of PD.

Polymorphism of the COMT, MAO, DAT, NET and 5-HTT Genes, and Biogenic Amines in Parkinson's Disease.

Epinephrine (E) and sympathetic nerve stimulation were described by Thomas Renton Elliott in 1905 for the first time. Dopamine (DA), norepinephrine (NE), E, and serotonin (5-HT) belong to the classic biogenic amines (or monoamines). Parkinson's disease (PD) is among the diseases in which it has been established that catecholamines may account for the neurodegeneration of central and peripheral catecholamine neural systems. PD is a chronic and progressive neurological disorder characterized by resting tremor, rigidity, and bradykinesia, affecting 2% of individuals above the age of 65 years. This disorder is a result of degeneration of DA-producing neurons of the substantia nigra and a significant loss of noradrenergic neurons in the locus coeruleus. In PD and other related neurodegerative diseases, catecholamines play the role of endogenous neurotoxins. Catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) catalyze the metabolism of monoamines. However, the monoamine transporters for DA, NE, and 5-HT namely DAT, NET, and SERT, respectively regulate the monoamine concentration. The metabolism of catecholamines and 5-HT involves common factors. Monoamine transporters represent targets for many pharmacological agents that affect brain function, including psychostimulators and antidepressants. In PD, polymorphisms of the COMT, MAO, DAT, NET, and 5- HTT genes may change the levels of biogenic amines and their metabolic products. The currently available therapies for PD improve the symptoms but do not halt the progression of the disease. The most effective treatment for PD patients is therapy with L-dopa. Combined therapy for PD involves a DA agonist and decarboxylase, MAOs and COMT inhibitors, and is the current optimal form of PD treatment maintaining monoamine balance.