Cure Alzheimer's Fund Cure Alzheimer's Fund

Alfred L. Goldberg, Ph.D.

Harvard Medical School

(1942–2023)

Dr. Goldberg, a professor of cell biology at Harvard Medical School, was on the faculty of that institution for nearly his entire academic career. His important discoveries concerned the biochemical mechanisms and physiological regulation of protein breakdown in cells and the importance of this process in human disease.  His laboratory first demonstrated the non-lysosomal ATP-dependent pathway for protein breakdown, now termed the ubiquitin-proteasome pathway. They first demonstrated the involvement of the 20S and 26S proteasomes in this process and discovered the ATP-dependent proteases responsible for protein degradation in bacteria and mitochondria.  Also of wide impact have been Dr. Goldberg’s studies showing that the ubiquitin proteasome pathway is critical in the clearance of misfolded proteins and in muscle atrophy seen in many disease states as well as in antigen presentation to the immune system.  He and his colleagues also first introduced proteasome inhibitors now widely used as research tools, and he initiated the development of the proteasome inhibitor, Bortezomib/Velcade, now widely used in the treatment of multiple myeloma.

Dr. Goldberg received his AB degree and his Ph.D. in Physiology in 1968 from Harvard University, after attending Cambridge University (as a Churchill Scholar) and Harvard Medical School.  Dr. Goldberg’s accomplishments were recognized with many distinguished prizes, including the Novartis-Drew Award, Severo Ochoa Award (New York University), Knobil Prize for Medical Research (Univ Texas, the Gabbay Award for Biotechnology and Medicine (Brandeis University), Norman Alpert Prize for Medical Research (Harvard), and Ernest Beutler Prize for Basic Research (Amer Hematology Soc.). He was a fellow of the American Academy of Arts & Sciences and a member of the National Academy of Sciences and the National Institute of Medicine. He received honorary degrees from Cold Spring Harbor Laboratories, the Univ of Maastricht (Netherlands) and Univ. of Barcelona (Spain) and was among the 1% most cited authors in the life sciences.

Related Research:

Activation of the 26S Proteasome for the Treatment of Alzheimer’s Disease Alfred L. Goldberg 2016-04-28

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
Activation of the 26S Proteasome for the Treatment of Alzheimer’s Disease 2016 to 2019

$645,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Yu, Z. Q., Carmichael, J., Collins, G. A., D'Agostino, M. D., Lessard, M., Firth, H. V., Harijan, P., Fry, A. E., Dean, J., Zhang, J., Kini, U., Goldberg, A. L., & Rubinsztein, D. C. PSMC5 insufficiency and P320R mutation impair proteasome function, Human Molecular Genetics, May 22, 2024, Read More

Lee, D., & Goldberg, A. L. 26S proteasomes become stably activated upon heat shock when ubiquitination and protein degradation increase, Proceedings of the National Academy of Sciences of the United States of America, June 21, 2022, Read More

VerPlank, J. J. S., Lokireddy, S., Zhao, J., & Goldberg, A. L. 26S Proteasomes are rapidly activated by diverse hormones and physiological states that raise cAMP and cause Rpn6 phosphorylation, Proceedings of the National Academy of Sciences of the United States of America, March 5, 2019, Read More

Collins, G. A., & Goldberg, A. L. Proteins containing ubiquitin-like (Ubl) domains not only bind to 26S proteasomes but also induce their activation, Proceedings of the National Academy of Sciences of the United States of America, March 3, 2020, Read More

VerPlank, J. J. S., Tyrkalska, S. D., Fleming, A., Rubinsztein, D. C., & Goldberg, A. L. cGMP via PKG activates 26S proteasomes and enhances degradation of proteins, including ones that cause neurodegenerative diseases, Proceedings of the National Academy of Sciences of the United States of America, June 8, 2020, Read More

Lee, D., Takayama, S., & Goldberg, A. L. ZFand5/ZNF216 is an activator of the 26S proteasome that stimulates overall protein degradation, Proceedings of the National Academy of Sciences of the United States of America, September 25, 2018, Read More

Kim, H. T., & Goldberg, A. L. UBL domain of Usp14 and other proteins stimulates proteasome activities and protein degradation in cells (vol 115, pg E11642, 2018), Proceedings of the National Academy of Sciences of the United States of America, November 28, 2018, Read More

Goldberg, A. L., Kim, H. T., Lee, D., & Collins, G. A. Mechanisms That Activate 26S Proteasomes and Enhance Protein Degradation, Biomolecules, May 22, 2021, Read More

VerPlank, J. J. S., & Goldberg, A. L. Regulating protein breakdown through proteasome phosphorylation, Biochemical Journal, September 24, 2017, Read More

VerPlank, J. J. S., Gawron, J., Silvestri, N. J., Feltri, M. L., Wrabetz, L., & Goldberg, A. L. Raising cGMP restores proteasome function and myelination in mice with a proteotoxic neuropathy, Brain, August 11, 2021, Read More

Collins, G. A., & Goldberg, A. L. The Logic of the 26S Proteasome, Cell, May 18, 2017, Read More

Kim, H. T., & Goldberg, A. L. The deubiquitinating enzyme Usp14 allosterically inhibits multiple proteasomal activities and ubiquitin-independent proteolysis, Journal of Biological Chemistry, June 9, 2017, Read More

Collins, G. A., Sha, Z., Kuo, C. L., Erbil, B., & Goldberg, A. L. Mammalian Ddi2 is a shuttling factor containing a retroviral protease domain that influences binding of ubiquitylated proteins and proteasomal degradation, Journal of Biological Chemistry, March 28, 2022, Read More

Sha, Z., Blyszcz, T., González-Prieto, R., Vertegaal, A. C. O., & Goldberg, A. L. Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies, Journal of Biological Chemistry, July 8, 2019, Read More

Kim, H. T., Collins, G. A., & Goldberg, A. L. Measurement of the Multiple Activities of 26S Proteasomes, Methods in Molecular Biology, September 22, 2018, Read More

Lee, D., Zhu, Y., Colson, L., Wang, X., Chen, S., Tkacik, E., Huang, L., Ouyang, Q., Goldberg, A. L., & Lu, Y. Molecular mechanism for activation of the 26S proteasome by ZFAND5, Molecular Cell, August 17, 2023, Read More

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