Alice Lazzarini

Last updated
Alice Lazzarini
Lazzarini 1992.png
Lazzarini in 1990
Known for Parkinson's disease research
Scientific career
FieldsGeneticist
Institutions Robert Wood Johnson Medical School
Website Lazzarini's blog

Alice M. Lazzarini is a scientist, author and researcher on neurogenetic disorders, including Huntington's disease and Parkinson's disease. She is an assistant professor of Neurology at Rutgers Robert Wood Johnson Medical School (RWJMS, previously known as University of Medicine and Dentistry of New Jersey or UMDNJ), [1] [2] where her work helped establish the genetic basis of Parkinson's. [3] Later in life, she was diagnosed with Parkinson's—the very disease she had spent decades researching. [4]

Contents

Huntington's disease

Lazzarini is a geneticist, [5] who worked in New Jersey as a genetics counselor and coordinator at Middlesex General-University Hospital's Huntington's Disease Family Service Center, serving individuals with HD and their families. [6] The News Tribune said in 1985 that it was "one of a handful of multi-disciplinary facilities in the country where various specialists join[ed] forces to address the problems faced by victims and their relatives ... serv[ing] more than 200 families since its opening in 1979". [6] Lazzarini helped lobby the New Jersey assembly for a bill to establish a residential facility for HD patients. [6]

Genetic disease research

Alice Lazzarini and Thomas Zimmerman with their poster for Machado-Joseph ataxia at the American Academy of Neurology meeting, 1992 Lazzarini Zimmerman 1992.jpg
Alice Lazzarini and Thomas Zimmerman with their poster for Machado-Joseph ataxia at the American Academy of Neurology meeting, 1992

Lazzarini was recruited in 1990 [3] to study ataxia as part of the RWJMS new William Dow Lovett Center for Neurogenetics. [7] In the early 90s, she was a member of the team studying neurodegenerative syndromes including olivopontocerebellar atrophy [8] (a degeneration of neurons in the brain present in syndromes such as Machado-Joseph disease) and spinocerebellar ataxia (SCA). [9] To study the causes of SCA, the researchers first had to locate a family having a large number of members with the disease; according to UMDNJ, Lazzarini "established a pedigree that may be the largest in North America". [9] One of Lazzarini's patients had located family records that led to a hundreds of individuals in one family encompassing eight generations and including 21 members who had the disease. [9] Lazzarini located another physician who was following a distant cousin of the same family, yielding a combined pedigree of thousands of family members dating to the 17th century. [9] [10] In the 1995 "W" Family Newsletter published by the UMDNJ-RWJMS Department of Neurology, Division of Neurogenetics, Lazzarini wrote: "We have found the 'W' [Whipple] family gene! ... [11]

While observing large family trees with many individuals having ataxia, Lazzarini noticed that many family members also had restless legs syndrome. [8] Lazzarini is published in the fields of X-linked intellectual disability and other neurologic disorders such as restless legs syndrome, Charcot–Marie–Tooth disease, and prion diseases. She has been a contributor as well to the literature on genetic counseling. [12]

Parkinson's disease

Lazzarini was a member of The GenePD Study, a 20-site research collaboration to identify genetic factors influencing Parkinson disease (PD). [13] Studying familial aggregation in a large group of family members with PD, she determined that a subset of Parkinson's cases are familial. [14] She was the head author on a paper published in 1994 pinpointing a genetic component to PD; [3] [15] according to the UMDNJ Science blog, "she defined the pattern of inheritance in 80 multicase families". [3]

Years earlier, the neurology clinic at RWJMS had located a family of Italian origin that encompassed at least five generations of more than 400 individuals and at least 60 members with PD. [14] Lazzarini began studying the family [16] whose ancestors were traced to the small village of Contursi, Italy. [14] In 1995, the RWJMS team joined with the National Center for Human Genome Research at the National Institutes of Health to take advantage of the laboratory resources available from the NIH in an effort to locate the gene causing PD in the Contursi family. [14] Collecting samples from patients in Italy, Lazzarini was a member of the team that reported the first Parkinson disease-causing mutation (PARK1) in the brain protein, alpha-synuclein. [17] [18] Lazzarini worked with the Italian Instituto de Scienze Neurologiche to get blood samples from the family members in Italy whose relatives in the US were also being studied; [19] she "pounded the pavement" to get samples from strangers, sometimes meeting resistance. [19] Once she "witnessed what seemed to be a vicious argument, carried out in Italian with hand gestures aplenty"; the 80-year-old woman whose sample was needed was afraid of needles, but eventually allowed her blood to be taken. [19]

The findings by the team, including scientists from the NIH and UMDNJ-RWJMS, [3] were published in Science magazine. [18] The New York Times reported that "scientists said that finding a site for the gene should help in finding other genetic factors that contribute to Parkinson's disease, which should eventually help in developing diagnostic tests and treatments". [20] [21] For ten years, Lazzarini and her colleagues had studied several generations of the large Italian-American family to establish the genetic basis of PD; [3] "they believed[d] that fragments of alpha-synuclein bind to other proteins to form the Lewy body, an insoluble proteinaceous material characteristic of Parkinson's disease". [14] In less than a year, the NIH and the UMDNJ-RWJMS team of Roger Duvoisin, William Johnson, Lawrence Golbe and Alice Lazzarini, working with the NIH and colleagues in Italy, had linked PD to DNA markers on chromosome 4. [22] Within days of the publication of the PARK1 findings, alpha-synuclein was discovered to be the major component of Lewy bodies within brain cells of PD patients; according to the UMDNJ magazine, "This discovery changed the direction of research into PD by providing scientists with an entirely new protein whose manufacture, function or breakdown could be the key to the disease." [23]

Personal life

Lazzarini was diagnosed with PD, the very disease she had spent a decade researching. [4] She published a memoir [24] chronicling her journey since being diagnosed.

Related Research Articles

Lewy body Spherical inclusion commonly found in damaged neurons

Lewy bodies are the inclusion bodies – abnormal aggregations of protein – that develop inside nerve cells affected by Parkinson's disease (PD), the Lewy body dementias, and some other disorders. They are also seen in cases of multiple system atrophy, particularly the parkinsonian variant (MSA-P).

University of Medicine and Dentistry of New Jersey

The University of Medicine and Dentistry of New Jersey (UMDNJ) was a state-run health sciences institution of New Jersey, United States.

Multiple system atrophy Neurodegenerative disorder

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum.

Parkin (protein)

Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the PARK2 gene. Parkin plays a critical role in ubiquitination – the process whereby molecules are covalently labelled with ubiquitin (Ub) and directed towards degradation in proteasomes or lysosomes. Ubiquitination involves the sequential action of three enzymes. First, an E1 ubiquitin-activating enzyme binds to inactive Ub in eukaryotic cells via a thioester bond and mobilises it in an ATP-dependent process. Ub is then transferred to an E2 ubiquitin-conjugating enzyme before being conjugated to the target protein via an E3 ubiquitin ligase. There exists a multitude of E3 ligases, which differ in structure and substrate specificity to allow selective targeting of proteins to intracellular degradation.

Spinocerebellar ataxia Medical condition

Spinocerebellar ataxia (SCA) is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a neurological condition in its own right. An estimated 150,000 people in the United States have a diagnosis of spinocerebellar ataxia at any given time. SCA is hereditary, progressive, degenerative, and often fatal. There is no known effective treatment or cure. SCA can affect anyone of any age. The disease is caused by either a recessive or dominant gene. In many cases people are not aware that they carry a relevant gene until they have children who begin to show signs of having the disorder.

Neurodegenerative disease Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

Contursi Terme is a village and comune in the province of Salerno in the Campania region of south-western Italy.

I-cell

Fritz Heinrich Jakob Lewy, a German-American neurologist, first identified and described inclusions in the brain cells of patients with Parkinson’s disease and published his findings in the Lewandowsky’s Handbook of Neurology in 1912. I-cells also called inclusion cells are abnormal fibroblasts having a large number of dark inclusions in the cytoplasm of the cell. They are metabolically inactive structures of a cell and are not enclosed by a membrane. The inclusions are of various fats, proteins, carbohydrates, pigments, excretory products, crystals, and other insolubles. They are found in the cytoplasm of a cell in both prokaryotes and eukaryotes. They are seen in Mucolipidosis II, and Mucolipidosis III, also called inclusion-cell or I-cell disease where lysosomal enzyme transport and storage is affected.

Beta-synuclein

Beta-synuclein is a protein that in humans is encoded by the SNCB gene.

Neurogenetics

Neurogenetics studies the role of genetics in the development and function of the nervous system. It considers neural characteristics as phenotypes, and is mainly based on the observation that the nervous systems of individuals, even of those belonging to the same species, may not be identical. As the name implies, it draws aspects from both the studies of neuroscience and genetics, focusing in particular how the genetic code an organism carries affects its expressed traits. Mutations in this genetic sequence can have a wide range of effects on the quality of life of the individual. Neurological diseases, behavior and personality are all studied in the context of neurogenetics. The field of neurogenetics emerged in the mid to late 20th century with advances closely following advancements made in available technology. Currently, neurogenetics is the center of much research utilizing cutting edge techniques.

Parkinsons disease Long-term degenerative neurological disorder

Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms become more common. The most obvious early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Cognitive and behavioral problems may also occur with depression, anxiety, and apathy occurring in many people with PD. Parkinson's disease dementia becomes common in the advanced stages of the disease. Those with Parkinson's can also have problems with their sleep and sensory systems. The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain, leading to a dopamine deficit. The cause of this cell death is poorly understood, but involves the build-up of misfolded proteins into Lewy bodies in the neurons. Collectively, the main motor symptoms are also known as parkinsonism or a parkinsonian syndrome.

History of Parkinsons disease History of Parkinsons disease

The history of Parkinson's disease expands from 1817, when British apothecary James Parkinson published An Essay on the Shaking Palsy, to modern times. Before Parkinson's descriptions, others had already described features of the disease that would bear his name, while the 20th century greatly improved knowledge of the disease and its treatments. PD was then known as paralysis agitans. The term "Parkinson's disease" was coined in 1865 by William Sanders and later popularized by French neurologist Jean-Martin Charcot. Paralysis

Mark A. Gluck is a professor of neuroscience at Rutgers–Newark in New Jersey, director of the Rutgers Memory Disorders Project, and publisher of the public health newsletter, Memory Loss and the Brain. He works at the interface between neuroscience, psychology, and computer science, studying the neural bases of learning and memory. His research spans numerous methodologies, including neurocomputational modeling, clinical studies of brain-damaged patients, functional and structural brain imaging, behavioral genetics, and comparative studies of rodent and human learning. He is the co-author of Gateway to Memory: An Introduction to Neural Network Models of the Hippocampus and an undergraduate textbook Learning and Memory: From Brain to Behavior.

Andrew Singleton British neurogeneticist

Andrew B. Singleton is a British neurogeneticist currently working in the USA. He was born in Guernsey, the Channel Islands in 1972, where he lived until he was 18 years old. His secondary education was conducted at the Guernsey Grammar School. He earned a first class degree in Applied Physiology from Sunderland University and his PhD in neuroscience from the University of Newcastle upon Tyne where he studied the genetics of Alzheimer's disease and other dementias at the Medical Research Council (MRC) Neurochemical Pathology Unit. He moved to the United States in 1999, where he began working at the Mayo Clinic in Jacksonville, Florida studying the genetic basis of Parkinson's disease, ataxia, and dystonia. He moved to the National Institutes of Health in 2001 to head the newly formed Molecular Genetics unit within the Laboratory of Neurogenetics. In 2006 he took over as Chief of the Laboratory of Neurogenetics and became an NIH Distinguished Investigator in the intramural program at the National Institute on Aging (NIA) in 2017. In 2020 he stepped down as the Chief of the Laboratory of Neurogenetics and became the Acting Director of the newly formed Center for Alzheimer's and Related Dementias at the NIA. In 2021 he became the Director of CARD.

Parkinson's disease (PD) is a degenerative disorder of the central nervous system. Most people with PD have idiopathic Parkinson's disease. A small proportion of cases, however, can be attributed to known genetic factors. Other factors such as environmental toxins, herbicides, pesticides, and fungicides, have been associated with the risk of developing PD, but no causal relationships have been proven.

Gene therapy in Parkinson's disease consists of the creation of new cells that produce a specific neurotransmitter (dopamine), protect the neural system, or the modification of genes that are related to the disease. Then these cells are transplanted to a patient with the disease. There are different kinds of treatments that focus on reducing the symptoms of the disease but currently there is no cure.

Maria Grazia Spillantini, is Professor of Molecular Neurology in the Department of Clinical Neurosciences at the University of Cambridge. She is most noted for identifying the protein alpha-synuclein as the major component of Lewy bodies, the characteristic protein deposit found in the brain in Parkinson's disease and dementia with Lewy bodies. She has also identified mutations in the MAPT gene as a heritable cause for frontotemporal dementia.

Synucleinopathy Medical condition

Synucleinopathies are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimer's Disease exhibit α-synuclein positive Lewy pathology, and are sub-classed as Alzheimer's Disease with Amygdalar Restricted Lewy Bodies (AD/ALB).

Animal models of Parkinsons disease Models used in Parkinsons disease research

Animal models of Parkinson's disease are essential in the research field and widely used to study Parkinson's disease. Parkinson's disease is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of the dopamine neurons in the brain, results in motor dysfunction, ultimately causing the four cardinal symptoms of PD: tremor, rigidity, postural instability, and bradykinesia. It is the second most prevalent neurodegenerative disease, following Alzheimer's disease. It is estimated that nearly one million people could be living with PD in the United States.

Hilal Lashuel is an American-Yemeni neuroscientist and chemist, currently an associate professor at the EPFL. His research focuses on protein misfolding and aggregation in the pathogenesis of Alzheimer's and Parkinson's diseases.

References

  1. ↑ "Notebook". The Scientist. December 9, 1996. Retrieved December 9, 2013.
  2. ↑ "Neurology: Faculty directory". Rutgers Robert Wood Johnson Medical School. Retrieved December 20, 2013.
  3. 1 2 3 4 5 6 "NIH and UMDNJ researchers localize gene for Parkinson's disease". Science Blog. University of Medicine and Dentistry of New Jersey. 1996.
  4. 1 2 "Parkinson's researcher gets Parkinson's: welcome to my home". Alice Lazzarini personal blog. Retrieved December 14, 2013.
  5. ↑ "Search For the Gene". UMDNJ Magazine. University of Medicine and Dentistry of New Jersey. Fall 1995.
  6. 1 2 3 Sullivan, G. Gary (February 1, 1985). "Huntington's families watch—and wait". The News Tribune. Woodbridge, New Jersey.
  7. ↑ Infeld, Karen (November 15, 1996). "NIH and UMDNJ researchers localize gene for Parkinson's disease" (Press release). University of Medicine and Dentistry of New Jersey. Retrieved December 9, 2013.
  8. 1 2 Witlow, Joan (February 24, 1991). "Scientists seek cure for OPCA: Patient's family tree yields clues to genetic ailment". The Star-Ledger. New Jersey.
  9. 1 2 3 4 "Family tree proves fruitful". HealthState. UMDNJ. Spring 1992. pp. 6–7.
  10. ↑ Lazzarini A, Zimmerman TR, Johnson WG, Duvoisin RC (November 1992). "A 17th-century founder gives rise to a large north American pedigree of autosomal dominant spinocerebellar ataxia not linked to the SCA1 locus on chromosome 6". Neurology. 42 (11): 2118–24. doi:10.1212/WNL.42.11.2118. PMID   1436521. S2CID   26020032.
  11. ↑ Lazzarini A (Spring 1995). "W". UMDNJ-Robert Wood Johnson Medical School Family Newsletter. 3 (1).
  12. ↑ Lazzarini A, Lou JQ (2002). "Genetic Counseling". In Lou, Jennie Q (ed.). Genetics challenges and opportunities for health care professionals. Dubuque, IA: Kendall/Hunt Publishing Company. pp. 63–84.
  13. ↑ DeStefano AL, Golbe LI, Mark MH, Lazzarini AM, et al. (Sep 2001). "Genome-wide scan for Parkinson's disease: the GenePD Study". Neurology. 57 (6): 1124–6. doi:10.1212/WNL.57.6.1124. PMID   11571351. S2CID   73219122.
  14. 1 2 3 4 5 "Eureka! They've done it again!". HealthState. UMDNJ. Fall 1997. pp. 6–7.
  15. ↑ Lazzarini AM, Myers RH, Zimmerman TR, et al. (March 1994). "A clinical genetic study of Parkinson's disease: evidence for dominant transmission". Neurology. 44 (3 Pt 1): 499–506. doi:10.1212/WNL.44.3_Part_1.499. PMID   8145922. S2CID   25443805.
  16. ↑ Ross, Lilla (November 26, 1996). "Local family's gift resulted in Parkinson's breakthrough". Florida Times Union. Jacksonville, Florida. p. E4.
  17. ↑ Groves, Bob (November 15, 1996). "N.J. cousins could hold key to Parkinson's: possible genetic link discovered". The Record. Bergen County, NJ. p. A1.
  18. 1 2 Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (June 1997). "Mutation in the alpha-synuclein gene identified in families with Parkinson's disease". Science. 276 (5321): 2045–7. doi:10.1126/science.276.5321.2045. PMID   9197268.
  19. 1 2 3 MacPherson, Kitta (November 15, 1996). "Unlocking Secrets of Parkinson's". The Star-Ledger. New Jersey.
  20. ↑ Leary, Warren E (November 15, 1996). "Scientists identify site of gene tied to some cases of Parkinson's". New York Times. Retrieved December 9, 2013.
  21. ↑ "Family gene is linked to Parkinson's disease". New York Times. June 27, 1997. Retrieved December 9, 2013.
  22. ↑ "One major step forward for Parkinson's sufferers". HealthState. UMDNJ. Winter 1997. p. 10.
  23. ↑ Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (August 1997). "Alpha-synuclein in Lewy bodies". Nature. 388 (6645): 839–40. Bibcode:1997Natur.388..839G. doi: 10.1038/42166 . PMID   9278044.
  24. ↑ Lazzarini, Alice (2014). Both Sides Now. privately published, CreateSpace Independent Publishing Platform. ISBN   9781475136982.
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